My opinion

By Dr. Iresh R Bhattacharjee
Corresponding Author Dr. Iresh R Bhattacharjee
Institute for Instrinsic Gravitation Biology (i3GB) {Assam Agricultural University}, 84,GMCH Road, Anandanagar, Dispur, Guwahati-781 005 India {C/O L.Dr.G.C.Bhattacharjee, Longai Road, Karimganj-788712, India} - India 781005
Submitting Author Dr. Iresh R Bhattacharjee

Gravity, gravitational potential energy, metabolic energy, buoyant force, self organization, astrophysics

Bhattacharjee IR. Self Gravity: The Major Investigation Gap in Life Science (Part I). WebmedCentral BIOPHYSICS 2013;4(6):WMC004279
doi: 10.9754/journal.wmc.2013.004279

This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Submitted on: 26 Jun 2013 11:08:44 AM GMT
Published on: 27 Jun 2013 07:36:00 AM GMT


Potential binding energy of self gravity acts universally on mass which is being ignored in living world at mesoscopic length scale without tangible reason. It is conceptualized that biomass accumulated through photosynthesis and other build-up mechanism within volume of secluded structure serve as foundation. Within membrane bound volume of mass, build up and break down mechanism through anabolism and catabolism of metabolic energy causes a change in the amount of mass per unit volume at particular instant leading to contraction out of gravitational potential energy and relaxation due to inertia plus kinetic energy of metabolic activity, develops pressure with gain or release of temperature. Background tension within volume causes mass to move asynchronously at low frequencies and continues to function as ‘life’. Kinetic energy producing organelles (mitochondria, chloroplast) remain away from central load. Self gravity attracts denser materials to its core leading to sorting and self assembling of mass according to density-gradient of macromolecules. Nucleic acid having higher density finds place as ‘core’, medium denser protein in intermediate and least dense fat in the periphery.  Metabolically inert infrastructure or buoyant force of fluids secludes self gravitating body from external stronger gravitational field and helps to maintain self gravity’s free fall condition. With collapse of equilibrium between contraction and relaxation of self gravity, stronger force of extrinsic gravity makes living mass inert non-living.

Under the principle of abductive reasoning through successive approximation on sporadic set of observations, roles of self gravity on identical astrophysical principles of larger mass have been conceptualized on some evidences detailed in Part I and II of the article. Various interior dynamics including self organization of macromolecules, protein conformation, movement of human thoracic diaphragm, formation of logarithmic spiral in nature were discussed in the light of potential energy of self gravity and kinetic energy of metabolic energy.




1. Self organization- intrinsic property of self gravity
2. How self-gravity could be strong at miniature scale?
3. How binding action of self gravity could be a reckonable force in biomass?


4. Mechanism of seclusion from extrinsic gravity
5. Relative three tier reference frame
6. Buoyant like force maintain self gravity’s free fall condition
7. Reduced fluid level stop metabolism
8. Neutral buoyancy can apparently reduce the weight of living mass
9. Nanometer level free fall acceleration for femtometer size macromolecules
10. Buffering action through repelling electrostatic force
11. Metabolically inert infrastructure (MII) as cell’s seclusion environment
12. Behavior of living mass under different types of medium
13. Importance of medium vis-à-vis unperturbed self gravity               &nb sp;                & nbsp;       


14. Whether gravitational anchor is a criterion for manifestation as living?
15. Energy producing organelles or sites located away from the centre
16. Some anomalous hypothecations in health science
17. Body Mass Index (BMI)
18. Body Surface Area (BSA)
19. Basal Metabolic Rate (BMR)
                &n bsp;                                 &nbs p;                &n bsp;                     

20. Why central position is vital?
21. Why nucleoid, nucleolis or nucleus tend to remain in central position?
22. Generation of ‘muscle tone’ remains elusive in human physiology
23. ‘Build-up’ & ‘break-down’ mechanisms in living mass
24. Spectacular action of self gravity in muscle tone while living and not when dead
25. There is no complete loss of tone during paralysis
26. Tone is lost after death during pallor mortis and not while living
27. Intrinsic muscle tone is constantly maintained when living but loose after death
28. Edema occurs in lowers or dependant parts of the body after death
29. Intuitive model on generation of ‘background tone’
30. Abundance of logarithmic spiral in nature vis-à-vis self gravitating phenomena
31. Human average body frequency
32. Body cools down on death after loss of contraction-relaxation of self gravity
33. Which force regulates stretching and relaxation during oesophageal peristalsis?
34. What causes channel narrowed or dilated during trafficking?
35. Why nuclear-cytoplasmic ratio is important for health?
36. Matching inward wall pressure in cellular activity vis-à-vis self gravity
37. Mechanical loads and centrosome - microtubule organization
38. Inner cell mass (ICM) influences potency in stem cells?
39. Metacenter and floating principle
40. Neucleus and neucleolus- ‘core’ segment of the self gravitating interior
41. Change in concentric to eccentric nucleus under neutral buoyant condition
42. Prototype of interior dynamics of self gravitating biomass


43. Self organization due to self gravity
44. Formation of twin centre of mass on decrease in mutual attraction
45. Self gravity dictates self organization of macromolecules in living cell
46. Globular protein form and self gravity
47. Native conformation, denaturation & renaturation of protein and self gravity
48. Some exceptions to general rule
49. Spheroids fibrous protein and self gravity
50. Protein folding problem and topological property
51. Proteins fold on funnel-shaped energy landscapes  



The trend among biologists is to describe any unexplained phenomenon as the gift of nature. This is irritating for any sensible person. Nature cannot act in self styled manner. It must obey certain defined physical rules. Hence such outlook needs appropriate correction. We must find continuity in the formation of the universe, the galaxy, the solar system to a tiny creature up to smallest bacteria or plasmid. What could be the force or factor that keeps such continuity from macro to meso or up to micro length scale? For instance, it is said that bilateral symmetry in animals is due to necessity to cope up with the environment. Personally you or I feel the necessity of having ‘third hand’ or ‘third eye’ in the backside to ward off many disadvantages we feel daily. The phenomena of bilateral symmetry are often described as ‘natural’. Why nature should act spontaneously? Similarly, say, muscle tone or background tensions remain elusive in human physiology. Tone works 24 hours a day. When muscles are at rest, a certain amount of tautness usually remains. Contraction in healthy human muscle tone is minimum 5 pulses per second. Electromyograph evidence shows that the muscle is electrically silent. Low frequency tone cannot be detected by electromyography.  Some quarter suspects that muscle tissue itself has an intrinsic elasticity. But if that were true, we would have to be fighting against that elasticity every time we used a skeletal muscle. Again all muscle contraction begins in the muscle core. Even in flat muscles contraction starts in the central plane, and then works its way out. Why muscle contraction begins in the muscle core? Similarly many other questions in life science are still not appropriately answered or if answered, these are difficult to digest in absence of supporting reasoning. In the same way, for instance, over the issue of ‘self organization’ in the cell, life science is passing through a major crisis. A living cell is not an aggregate of molecules but an organized pattern, structured in space and in time. Harold M Franklin1 in 2005 made extensive reviews on the spatial organization of cells, including the arrangement of cytoplasmic constituents and the cells' global form, which is not explicitly spelled out in the genome. Genes specify only the primary sequences of macromolecules, portions of which are indeed relevant to the localization of those molecules in space. But cell architecture, for the most part, arises epigenetically. What could be the invisible epigenetic mechanism that could be the driving force and builds up organic complexity in a membrane-bound, structured setting and lead to spontaneous self-emergence of spatially organized systems from where molecules come to life?

Working on range of paradoxes in biology, on critically examining various reported works on these aspects, on undertaking strategic experimentations and observing on diverse living organisms randomly but in a purposeful meticulous way for last 40 years from ab initio stage to intermediate and final status, during intact state (in vivo), under removed condition (ex vivo) as well as in vitro culture of various living organisms and on  carefully avoiding  over-interpretation that may not lead to erroneous conclusions, I came to the approximation that presence of intrinsic gravity or in other words, self gravity, an invisible binding force that holds the body structures in place or is responsible primarily for ‘self organization’, building up of low frequency but steady muscle tone is difficult to ignore. Gravity is the building block of the universe. The reality of the cellular interior might be determined by the equilibrium between ‘build up’ and ‘break down’ of mass leading to its gain or loss. A reversible mechanism between kinetic and potential gravitational energy due to variation in instant mass might create internal pressure. Such internal pressure might work against self gravitational compression. The surrounding hydrostatic pressure might help to create self gravitating environment around a living mass.  This is also what is going on in the interior of the universe, in the galaxy, in the star, the sun, the planet and the moon. The materials may differ but all works might be on the same principle of equilibrium between internal pressure and gravitational pressure. The equilibrium or balance might be the law of life from universe to living bodies.

As per concept of molecular biology, DNA sequences are transcribed into RNA and then translated into amino acid chains; the latter fold spontaneously into functional proteins. But genesis of spatial architecture, including how molecules find their proper location in cell space, the origins of supramolecular order, cell morphology are not yet satisfactorily answered. Harold M Franklin1 therefore concluded that “We urgently need a plausible and experimentally fertile hypothesis that starts with a driving force and builds up organic complexity in a membrane-bound, structured setting. No satisfying hypothesis of this kind is presently on the books, and in its absence holistic explorers of deep time have been unable to initiate a research tradition that can thrive in today's intellectual and fiscal climate. But I have no doubt that this is the way to go; for only through the emergence of spatially organized systems can molecules come to life”. From all such gap areas of investigations, the present study was undertaken to define the role of self gravity in living mass. 

Physical Property of Self Gravity

1. Self organization- intrinsic property of self gravity

To understand nature of self gravity, Prof. J.V. Narlikar2, eminent astrophysicist, used an imaginary episode from the life of Aladdin. The Arabian Nights story of Aladdin and the magic lamp ends with Aladdin living “happily even after” with his princess and his magic lamp. But one hot summer’s day, Aladdin, while on a tour of the Arabian Desert suffered sunstroke. He summoned the genie of the magic lamp and issued command “Take the Sun apart and distribute its bits and pieces far and wide so that it is completely destroyed”. Genie started chipping off bits and pieces from the surface of the Sun. He has to work against the force of gravity ( ), where G is the gravitational constant; M is mass and R is radius). Aladdin began to have a second thought. He realized how essential the Sun was to the inhabitants of the Earth, including himself. So, while the genie was in the process of completing the job, Aladdin issued his next command: “Put all the bits of the Sun back together”. The poor genie went back to execute the command. However, this time, to bring all the constituents of the Sun together, the genie no longer had to work against the gravity. In fact, while the genie had been temporarily called away by Aladdin to issue his second command, the bits and pieces left in space by the genie had already began to fall back together. Self gravity, which had been a opposing force for the first job, had now turned into an ally. And to put the Sun back together, the genie had to do no work. Instead, the amount of work, which the genie had earlier expended on the first job against the force of self gravity, would now be done by the force of self gravity to put the Sun back together (illustration 1). So from the imaginary story above it is clear that the self gravity is the natural inward compressive force having potential energy for which genie had nothing to do to put sun in position. We will demonstrate how self gravity would be the binding force not only at organism level but even at macromolecular level.

2. How self-gravity could be strong at miniature scale?

Gravity is the invisible building block of the universe. Among the basic forces (nuclear, electro-magnetic & gravity), gravity acts on ‘mass as action at-a-distance’. Living organism without "mass" cannot be imagined. So effect of gravity in living mass cannot be ignored. Biology starts in the particle hierarchy in non-Newtonian state, with accumulation of ‘macromolecular mass’ at organelles or cell level3,4,9 (Illustration 2). The particle hierarchy shows sub-atom, atom, molecule, compound, organelles, cells, tissue, organ, organ system, and organism. Here we are to compare vital question on presence of competitive forces like electromagnetic, nuclear and elastic forces that could act as binding force at miniature scale. Both gravity and electromagnetism obey the inverse-square law, i.e. their strength declines by the square of the distance between interacting systems. In other respects, however, they seem to be very different. For instance, the gravitational force between two electrons is 42 orders of magnitude (1042) weaker than their electrical repulsion. The reason electromagnetic forces do not completely overwhelm gravity in the world around us is that most things are composed of an equal amount of positive and negative electric charges whose forces cancel each other out. Whereas electric and magnetic forces are clearly bipolar, gravity is generally assumed to be always attractive so that no analogous cancellations occur.  Gravity works on mass without any time frame, as if relatively constant like physical structure of a house. Electromagnetic force works on ‘charges’ in time bound manner, as if a relatively variable like an electric bulb based on off and on switch. All time supremacy of self gravity on mass as potential energy therefore cannot be ignored.

On the other hand, theoretical calculation shows that exertion of gravitational forces which follows inverse square law gets increased from 0.0007 to 6.6726 dynes when quantity in two masses increase from 10-4 to 10-2 grams under same separation distance of  10-6 centimeter (Illustration 3 Table 1). Similarly when separation distance is decreased from 10-6 centimeter to 10-10centimeter for the same two masses of 10-4 grams each, the gravitational force is increased from 0.0007 to 66,726 dyne (Illustration 4 Table 2).

Sizes of some biomass are mentioned below for ready reference. A prokaryotic cell of E.coli is about 2 µm or 2x10-6 m long, 1 µm wide, diameter 0.8 µm, wet weight 1x10-15 kg or 1x10-12 g, dry weight 3.0x10-16 kg or 3.0x10-13 g. Viruses range in between 30 to 300 nm or 300 to 3000 A0 in size. The protein comprising a prion has a molecular weight between 50,000 to 100,000, corresponding to a particle size that is 100 times smaller than the smallest virus. Micoplasmas range in size (diameter) from 0.25 to 0.1 µm. Even with such miniature size, force of gravity cannot become extinct. With higher density of mass, gravitational potential energy gets increase. Interestingly living matter, unlike non-living, has got two categories of metabolism, anabolism that builds up mass and catabolism that breaks down mass of carbohydrates. Gravitational binding energy works on mass as potential energy whereas kinetic energy is created from such mass. The total human body content of ATP is about 50 grams, which must be constantly recycled every day. The average daily intake of 2,500 food calories translates into a turnover of a whopping 180 kg of ATP. With breakdown of mass through catabolism, there would be a variation in the kinetic energy at an instant. It is a continuous process. When contacting surfaces move relative to each other due to potential and kinetic energy, a pressure is developed out of friction with rising of temperature. Researchers have found that basal metabolic rate (BMR) or amount of energy expended for an organism is proportional to Mass 2/3 to ¾.  There is a strong relation of mass with gravitational energy and metabolic rate in living organism. This is a major gap area of investigation in life science to correlate potential gravitational energy and metabolic kinetic energy from the same amount of mass.

3. How binding action of self gravity could be a reckonable force in biomass?

Gravity is customarily considered as long distance force acting on massive body. But in fact, biology starts in non-Newtonian state as soft condensed matter in which the viscosity changes with the applied shear stress. Unlike fluid (say, water) which could return back to its original position after withdrawal of stress, soft matter displays a range of fascinating generic properties such as ability to ‘self assemble’ into complex structures, a large number of internal degrees of freedom, weak interactions between structural elements, and a large thermal fluctuations at room temperature, a wide variety of forms, sensitivity of equilibrium structures under metastable states to external conditions. The Newton’s inverse-square law would be valid if there is no additional dimension. However, if there are two additional dimensions, the dependence of the gravitational force would change from 1/r2 to 1/r4, or the gravitational potential could take the following form (Illustration 49 Equation 1 and 2):

If dividing by 1/r2 is a small number, dividing by 1/r4 (twice of 1/r2) can make the corresponding gravitational force much stronger5,6

On the other hand, gravitational binding energy of an object consists of the amount of energy required to pull all of the matters apart including amount of energy that is liberated in the form of rising temperature during the accretion of matters. The gravitational binding energy of a system is equal to the negative of the total gravitational potential energy, considering the system as a set of small particles. For a spherical mass of uniform density, the gravitational binding energy U is given by the formula7,8 (Illustration 49 Equation 3):

where G is the gravitational constant, M is the mass of the sphere, and r is its radius. But radial density gradients (ρ) of biological mass are not uniform. Normally there is lower density at the surfaces and comparatively higher density in the inner parts including compressed cores or nucleus, which we will mention subsequently. This needs to be evaluated with appropriate data. Therefore ignoring intrinsic gravity in living organism, as negligible force, is difficult under the present scenario. Gravity is not an instant force like others. Its manifestation is visible only at the later stage as an everlasting force.

Seclusion Maintains Self Gravity Free fall Condition

4. Mechanism of seclusion from extrinsic gravity

 Arguments came from physicists that stronger earth's gravity would swamp the intrinsic gravity of small biomass. But moon, being self gravitating body could retain its identity on seclusion even being swamped by the gravitational field of the earth, solar system or the universe. On close examination, clue can be found on seclusion for intrinsic gravity from extrinsic gravity. An egg floats on saline water, on working against earth's gravity, due to buoyant force (Illustration 5a). Buoyancy acts against the force of gravity and so makes objects seem lighter with respect to gravity. To represent this effect, which is important for sedimentation, it is common to define a buoyant mass mb that represents the effective mass of the object with respect to gravity (Illustration 49 Equation 4)

where mobject is the true (vacuum) mass of the object, whereas ρobject and ρfluid are the average densities of the object and the surrounding fluid, respectively. Thus, if the two densities are equal, ρobject = ρfluid, the object appears to be weightless. If the fluid density is greater than the average density of the object, the object floats; if less, the object sinks. Various ionic fluids including amniotic fluid secludes macromolecules or fetuses from earth’s gravity9,10,11 (Illustration 5b,5c). Fetuses develop on seclusion in near-weightless environment of mothers' wombs. During the last trimester, it turns upside-down with head-lower condition.

5. Relative three tier reference frame

Spaargaren (1994) coined the term ‘metabolically inert infrastructure’ (MII) 12 that consists of total body mass (body water, dissolved substances, mineral and organic deposits) and serves as storage of nutrients, transport and distribution of these materials. To act independently as living body, we propose that MII provide structural support for seclusion to the macromolecules or organisms with density-gradient buoyant force against extrinsic gravitational attraction for the biological mass.

Let self-gravitating biomass/ embryo, being powered by metabolic energy (ME) be in the accelerated reference frame, manifesting its physiological and genetic functionality.    ‘Metabolically Inert Infrastructure (MII)’ placed in the co-moving non-accelerated reference frame that are relatively stationary or at constant velocity, or non-aligned or acting in opposite direction of the energized accelerated self gravitating biomass or of the steady state supporting inertial reference frame at the specific  point of time13,14,15 (Illustration 6) .

The situation is similar to children playing ball within a compartment of a running train. Here ball is in the accelerated reference frame and compartment is in the non-accelerated reference frame which is pivoted through wheels over inertial reference frame of the ground earth (Illustration 7a, b). While playing, children cannot distinguish whether they are playing in the running compartment of train or in the stationary ground. In a moving but non-accelerating frame, the ball behaves normally because the train and its contents continue to move at a constant velocity. Before being dropped, the ball was traveling with the train at the same speed, and the ball's inertia ensured that it continued to move in the same speed and direction as the train, even while dropping. In fact it is inertia which ensured that, not its mass. Therefore if a given mass does not have the opportunity to interact with the surrounding forces, it would continue to act independently. The manifestation of various biological phenomena can be considered on the ‘principle of equivalence’16. Gravitational force field is a central field; the gravitational forces are directed toward the centre of the gravitating mass. These forces decrease in proportion to the square of the distance. Therefore self gravitating tiny biological mass under seclusion or near weightless condition can act in independent manner on the ‘principle of equivalence’ of larger mass.

6. Buoyant like force maintain self gravity’s free fall condition

We consider self gravity, central attracting force acting on mass under free fall condition. A membrane bound living cell has three-dimensional region composed of cytoplasmic matrix and other organelles. Under hydro-gravitational suspension, pressure gradient in the ?uid is not uni-directional. Archimedes principle estimate buoyancy on the basis of density of the solid and the density of the ?uid and is valid only when the pressure gradient in the ?uid is uni-directional and can be reduced to the constant of the form ∇ p = ρg, where ρ is the average density of the ?uid displaced by the submerged object and g is the gravity acceleration vector in the direction of the free fall of the object17,18. Only then the buoyancy force F becomes equal and opposite to the weight of the displaced ?uid W = ρgV. For a comparatively semi-solid macromolecules surrounded by near spherically symmetric pressure gradients (such as a cellular nucleus suspended in cellular interior) the estimation of the buoyancy force must include explicit integration of all pressure forces that act on the entire submerged surface of that object.

The divergence theorem (also called Gauss's theorem) 19 states that the total expansion of the fluid or gas inside some three-dimensional region W equals the total flux of the fluid or gas out of the boundary of W. In living cells, the definition of the divergence therefore follows naturally by noting that, in the absence of creation or destruction of matter, the density within a region of space can change only by having it flow into or out of the region. By measuring the net flux of content passing through a surface surrounding the region of space, it is therefore immediately possible to say how the density of the interior has changed. This property is fundamental in physics, where it goes by the name "principle of continuity"20. We propose that in biology, especially in living cell, such principles of continuity may also operate. Divergences at a given point describes the strength of the source or sink in the flow of fluid or gas representing expansion (positive) or compression (negative) of the vector field. Integrating the field's divergence over the interior of the region should equal the integral of the vector field over the region's boundary. For near spherically symmetric pressure gradients (such as a cellular nucleus suspended in cellular interior) the estimation of the buoyancy force must include explicit integration of all pressure forces that act on the entire submerged surface of that object. We will discuss the issue in details subsequently.

As per general model detailing concept of self gravitation bio, every living cell is compressed by invisible force of self gravity. As stated above, in biological particle hierarchy (atoms, molecules, compounds, organelles, cell, tissues, organs, organs system, organism), attractive central force of self gravity becomes prominent at the level of organelles over other basic forces (viz. electromagnetic and nuclear forces) while on seclusion. In general relativity, gravity is not regarded as a true force, but just as the manifestation of space-time’s geometry on the movement of matter and energy. In cosmology, λ (lambda - the cosmological constant) is frequently referred to as a sort of "negative gravity"21: instead of attractive it's repulsive, and instead of getting weaker with distance it gets stronger.  However we are not going details of controversy over the validity of such gravity.

7.  Reduced fluid level stop metabolism

The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. The entire contents of a eukaryotic cell, minus the contents of the cell nucleus, are referred to as the cytoplasm. Most of the cytosol is water, which makes up about 70% of the total volume of a typical cell 20. In eukaryotes this liquid is separated by cell membranes from the contents of the organelles suspended in the cytosol, such as the mitochondrial matrix inside the mitochondrion. The entire contents of a eukaryotic cell, minus the contents of the cell nucleus, are referred to as the cytoplasm. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others are contained within organelles.  The cytosol has no single function and is instead the site of multiple cell processes.  Studies in the brine shrimp (Illustration 8) have examined how water affects cell functions. It was found that reducing the amount of water in a cell below 80% of the normal level inhibits metabolism, with this decreasing progressively as the cell dries out and all metabolism halting at a water level about 30% of normal23. With inadequate depth of supporting fluids, macromolecular mass in the interior lost their gravitational seclusion identity. Kinetic energy of metabolism failed to overtake potential gravitational energy.

Why depth of fluid (below 80% of the normal) is important?  Density (d) is defined as the ratio of an object's mass (m) to its volume (v): d= m/v. The specific gravity of a substance is defined as the ratio of the density of the substance to the density of water (1 gram/cm3). This ratio is a convenient physical property since it has no units and is therefore independent of the system of measure used to determine it.  The Pascal’s law24, 25 invites the presence of entity of two bodies; first one is to dip on the other and pressure by it is to be applied to the enclosed liquid to express in transmitting equally to every part of the liquid (Illustration 9). Effect of change in height in the cytosol or fluid column within living architecture, as in Pascal’s law can be considered as gap areas of investigation in terms of potential and kinetic energy of gravitation and metabolism respectively. Is it what Harold M Franklin1 prompted to say that “of cellular morphogenesis … we know much but understand little.”

8. Neutral buoyancy can apparently reduce the weight of living mass

Neutral buoyancy is said to be a condition in which a physical body's density is equal to the density of the fluid in which it is immersed. This offsets the force of extrinsic gravity that would otherwise cause the object to sink. An object that has neutral buoyancy will neither sink nor rise. The actual mass of the human brain is about 1400 grams; however, the net weight of the brain suspended in the cerebrospinal fluid (CSF) is equivalent to a mass of 25 grams18 i.e. what is 56 gm in human body will appear to be 1 gram only under neutral buoyant condition of the brain. The brain exists in neutral buoyancy, which allows the brain to maintain its density without being impaired by its own weight, which would cut off blood supply and kill neurons in the lower sections without cerebrospinal fluid (CSF)26.

We know what is 6 kg on earth is 1 kg weight at moon. When a person arrives at moon, he will be acting as per external gravitational force of the moon and not as per that of earth. Accordingly a person when reaches moon feels lighter. A normal weight of a human child at birth is say 3200 gm on earth but at moon its weight would be 531 gm.

Amniotic fluid index (AFI) is a rough estimate of the amount of amniotic fluid27 and is an index for the fetal well-being. It is a part of the biophysical profile (Illustration 10).  AFI is the score (expressed in cm) given to the amount of amniotic fluid seen on pregnant uterus and calculated by a ultrasonograph To determine the AFI, doctors may use a four-quadrant technique 28, 29, when the deepest, unobstructed, vertical length of each pocket of fluid is measured in each quadrant and then added up to the others, or the so called "single deepest pocket" technique30. The linea nigra is used to divide the uterus into right and left halves. The umbilicus serves as the dividing point for the upper and lower halves. The transducer is kept parallel to the patient’s longitudinal axis and perpendicular to the floor. The deepest, unobstructed, vertical pocket of fluid is measured in each quadrant in centimeters 31. The four pocket measurements are then added to calculate the AFI. An AFI between 8-18 is considered normal. Median AFI level is approximately 14 from week 20 to week 35, when the amniotic fluid begins to reduce in preparation for birth. An AFI < 5-6 is considered as oligohydramnios. The exact number can vary by gestational age. The fifth percentile for gestational age is sometimes used as a cutoff value. An AFI > 20-24 is considered as polyhydramnios. What is the inner purpose of AFI?

9.  Nanometer level free fall acceleration for femtometer size macromolecules

Under secluded gravitating environment, nanometer level free fall acceleration would be a tremendous force for femtometer size macromolecules. Let us interpolate and visualize the phenomena with some superimposed data. Literature on neutral buoyant force of amniotic fluid and utero as well as ex utero measurements is scanty. Let us concentrate our attention to the works of Junwu Mu et al32 who made in vivo quantification of embryonic and placental growth during gestation in mice using micro-ultrasound and pair-wise comparisons of in utero and ex utero measurements. They reported that when gestational age of mice reaches 16.5 days, the non-invasive predictive body weight remains to 0.792 gm in average. The crown-rump length (CRL) and abdominal circumference (AC) was reported to be the function of gestation age (Illustration 11).  The CRL and AC remain to be 16.22 mm and 23.4 mm respectively at that growth stage of mice. The average radius of the fetus can thus be considered to be roughly 9.9 mm.

Let us extend theoretically the fetal weight floating over amniotic fluid on the same principle of loss of brain weight in cerebrospinal fluid. Ignoring difference in the value of neutral buoyancy in cerebrospinal and amniotic fluids, due to differential presence of salt and other matters, the neutral buoyant weight of mice embryo of 0.792 gm would appear to be 0.014gm.  The acceleration due to gravity on earth is about 9.8 m/s2, whereas at moon it is 1.62 m/s2. However, if we calculate acceleration due to (self) gravity in 0.792 gram at 16 days of gestational age of mice with radius 9.9 mm, separated by neutral buoyant force, as provided by  Junwu Mu et al[27], using standard formula g(s)= GM/R2, it comes to be about 5x10-9 m/s2. That is free fall acceleration to the tune of 5 nanometer per second square in a massive body of the planet may be negligible, but in an isolated living mass of the size 9.9 femtometer (9.9x10-12 meter), acceleration of 5 nm/s2 is quite a significant force. 

Soccer is being played by all ages. Age wise, playing standard, materials, circumference or weight of ball may differ.  For youth/adult, ball may be of leather having 70 cm circumference and 450 gram weight. For high school level students, circumference and weight of the ball may be reduced to 62 cm and 396 gram respectively. For kids, weight could be less than 100 grams. Everyone will play as per individual capabilities (Illustration 12). Similarly action of self gravity on earth can result an apple to fall on earth, or that of moon can cause a person to move easily when at moon. Similarly free fall acceleration at nanometer level would be tremendous for protein, fat or any macromolecule of femtometer size and should not be overlooked in tiny fetal body within its self gravitating mass. As such importance of operation of neutral buoyancy at cytosol or intracellular fluid (or cytoplasmic matrix) at cell level or amniotic fluid at mammalian level as mechanism for buffering pad to maintain self gravity’s free fall condition is difficult to ignore.

10.  Buffering action through repelling electrostatic force

Lipid bilayer is a universal component of all cell membranes (earlier it was designated as cell surface coat). The structure is called a "lipid bilayer" because it composed of two layers of fatty acids organized in two sheets. The lipid bilayer is typically about five nanometers to ten nanometers thick and surrounds all cells providing the cell membrane structure. With the hydrophobic tails of each individual sheet interacting with one another, a hydrophobic interior is formed and this acts as a permeability barrier 33. The hydrophilic head groups interact with the aqueous medium on both sides of the bilayer. The two opposing sheets are also known as leaflets. Due to electrostatic force, these double bonds inhibit "packing" of the molecules (in solids). Therefore in limited manner, the lipid bilayer may act as cushion or buffering pad for separation between gravity barriers of two gravitating bodies (self gravity and extrinsic gravity) under simultaneous operation and thereby possibly provides opportunity for secluded environment towards unhindered action of the self gravity.

11.  Metabolically inert infrastructure (MII) as cell’s seclusion environment

Cytoplasm is composed mainly of water and also contains enzymes, salts, organelles, and various organic molecules. As stated earlier Spaargaren (1994) coined the term ‘metabolically inert infrastructure’ (MII)12 to describe liquids in the cell. In unicellular organisms, cell’s environment- viz. a substratum beneath it, a liquid medium around it and neighboring cells beside it; whereas in multicellular organisms, aggregation of cells and tissues with sufficient intra and extra-cellular matrix in totality affect ‘life’, due to co-moving non-accelerated position of the metabolically inert infrastructure (MII) that are relatively stationary or at constant velocity, or non-aligned or acting in opposite direction of the energized accelerated self gravitating biomass or of the steady state supporting inertial reference frame at the specific  point of time. Thus MII seems to play anti (self) gravitational role. Without MII support death occurs (Illustration 13).

We propose few more examples of metabolically inert infrastructure, the exact role of which is so far not specified in life science. Algae, for instance, cannot multiply unless they get an adequate depth of liquid media. Bacteria cannot survive outside the cultural media. Virus cannot survive without the support of any living host. Transfer a gene from one chromosome to other is to be carried through plasmid or bacteriophage which is said to act as vehicle. In biotechnologies, an enzyme is to be coated in a porus gel or fixed to a solid support which acts as media. Similarly  solid support that contains substance usually a gel such as agar embedded in it for bacteria and yeast,  nutrient broth (liquid nutrient medium) or Luria Bertani medium (LB medium or Lysogeny Broth); extracellular matrix components ; calf serum; suspension cultures; polyacrylamide gels, collagen gels, and basement membrane gels at cell–substrate interface for glioblastoma; organotypic cultures; etc are some other examples that appears to maintain invisible separation between self gravity and mutual gravity or seclusion environment for self gravity. Intravenous drip of ‘isotonic saline’ to an ailing patient seems not only corrects disturbances in water and electrolytic balance but also provides in limited manner buoyancy force to various life supporting organs or systems against gravitational pressure. Mucilaginous jelly which surrounds the embryo in amphibians such as frogs, toads as well as in insects possibly acts in a similar way. Hence it can be said that role of metabolic inert infrastructure towards keeping secluded condition for operation of self gravity is a vital gap area of investigation in biological science.

12. Behavior of living mass under different types of medium

It is to be remembered that fluids play an important role towards buoyant like physical force that separate self gravitating biomass in living body from the surrounding inertial gravitational forces, else which might perturb the action of self gravity.  In addition to cytoplasmic and other fluid matrix in living cells, human body contains various fluids like blood plasma, lymphatic fluid, interstitial fluid, viscous fluid of mucus, saliva, gastric juice, cerebrospinal fluid, sweat, tears, the aqueous and vitreous humors of the eye, semen, vaginal secretions, amniotic fluids etc. The composition, density and depth of each fluid differ affecting operational buoyant force. For instance, brain exists in neutral buoyancy. The actual mass of the human brain is about 1400 grams; however, the net weight of the brain suspended in the CSF under neutral buoyancy is equivalent to a mass of 25 grams. Similarly blood cells are suspended in a fluid called blood plasma, which is mainly composed of water and a mixture of other dissolved substances, or solutes apart from hormones, vitamins, amino acids, and antibodies. Blood plasma has a density of approximately 1.025 kg/l. In comparison to plasma, glucose in cerebrospinal fluid (CSF) is diminished by about 80%.  It is a gap area of investigation that how far disturbance in operational buoyant force can perturb various activities of life processes.

Cells traditionally have been studied in two dimensions (2-D) in a petri dish, but certain cells behave differently in three dimensions than in two.  Size  and  shape  of  the  cell  depend  on  the  external  biophysical  forces. Cells exposed to microgravity include more rounding, loss of gravity-dependent convection, negligible hydro-dynamic shear and lack of sedimentation34. MIT bioengineers35 have provided pictures that show normal and diseased cartilage cells which are organized differently in normal and diseased cartilage and 3-D cell clusters of same normal and diseased cartilage precisely re-created in a tissue like gel compared to cells in a conventional 2-D petri dish (Illustration 14).  External biophysical force is to be examined critically for specifying behavior of the living mass on it, especially gravitating environment towards maintaining seclusion.

13. Importance of medium vis-à-vis unperturbed self gravity

We have assumed that self-gravitating biomass/ embryo is in the accelerated reference frame, manifesting its physiological and genetic functionality. The “Metabolically Inert Infrastructure (MII)? is placed in the co-moving non- accelerated reference frame that are relatively stationary or at constant velocity, or non-aligned or acting in opposite direction of the energized accelerated self gravitating biomass or of the steady state supporting inertial reference frame  at the  specific  point  of time.  Let us see how it applies in case of mediums required as microbial or biotechnological analysis protocols like agarose, polyacrylamide, silica colloidal crystal (SCC), raffinose etc. For instance,  three   “blot”  techniques  are   utilized   for  detecting  presence  and relative  quantities  of  specific macromolecules (DNA, RNA, protein) in cells viz. DNA (Southern) with agarose/ acrylamide, RNA (Northern) with agarose, and protein (Western) with polyacrylamide. Why to be positioned over agarose or other gel? The agarose gel is a cross-linked matrix that is somewhat like a three-dimensional mesh or screen36. When boiled agarose cools, it forms a loose molecular net resembling a sponge with required mechanical rigidity in soft porous texture. The pores in the gel matrix are filled by the liquid phase. Buoyant like force of the liquid is thus augmented by mechanical rigidity of the surrounding structure. Thus apart from other known advantages, final agarose gel gets the ability to withstand compressibility and allows the positioned biomass to feel less stressed under concentrated gravitational load (Illustrations 15).

In Southern blotting, for instance, after separation of fragments according to length, a sheet of either nitrocellulose paper or nylon paper is laid over the gel, and the separated DNA fragments are transferred to the sheet by blotting. The gel is supported on a layer of sponge in a bath of alkali solution, and the buffer is sucked through the gel and the nitrocellulose paper by paper towels stacked on top of the nitrocellulose (Illustration 16).

As the buffer is sucked through, it denatures the DNA and transfers the single -stranded fragments from the gel to the surface of the nitrocellulose sheet, where they adhere firmly. Stress applied from own weight and from external load is known as effective and net stress respectively. The bulk modulus of a substance, on the other hand, measures the substance's resistance to uniform compression or stress. For effective rafting, the biomass is required to be secluded, isolated or free from stress on flotation or through other mechanisms. Stress applied from own weight differs among RNA, DNA and protein fragments due to obvious reason of difference in molar mass and density. Also agarose gels have larger 'pores' than polyacrylamide gels meaning that it packs less densely then an equivalent amount of polyacrylamide. Therefore, considering variation in packing density, agarose is generally used for the electrophoresis of large molecules such as DNA and RNA and polyacrylamide is used for small molecules such as proteins. Uneven local mass distribution causes local variation in density as well as gravitational attraction. Accordingly choice for seclusion is being made among various available materials.

Evans et al37   pointed out that while cell attachment was unaffected by the stiffness of the growth substrate, cell spreading and cell growth were all increased as a function of substrate stiffness and the mechanical environment can play a role in both early and terminal embryonic stem cells (ESC) differentiation. Ji L et all38    found that  cells cultured on the substrates formed of silica colloidal crystal (SCC) retained transcription of stem cell and endoderm markers more similar to undifferentiated ESCs, suggesting the substrates are restricting differentiation, particularly towards the endoderm lineage, compared to cells cultured on flat glass. Additionally, five days after seeding, they observed strikingly different colony morphology, with cells on the SCC substrates growing in spherical colonies approximately ten cells thick, while cells on glass were growing in flat monolayers. Colonies on the SCC substrates developed a central pit, which was never observed in cells cultured on glass, and expressed proteins related to epithelialisation. Together, these data demonstrate the potential of using topographical cues to control stem cell behaviour in vitro. For smallest prion39, say ([Het-s] prion (molecular weight of 35-36kDa) of the filamentous fungus Podospora anserina transformants are grown in liquid raffinose synthetic medium (SR) plus galactose. As stated above, molar mass of raffinose, a trisaccharide composed of galactose, fructose, and glucose is 504.42 g/mol with density 1.723 g/cm3. Therefore it seems that medium plays a vital role towards unperturbed action of self gravity. For smallest prion, a protein, liquid reffinose, a carbohydrate is sufficient to increase density of the liquid medium and thereby provide a separation due to pressure of up thrust from inertial gravity, where as for DNA, RNA, larger proteins, whose molecular weight and density is comparatively higher, mechanical prop up support from agarose gels etc. is additionally required. However all these are gap areas of investigation.

Metabolic Energy and Self Gravity

14. Whether gravitational anchor is a criterion for manifestation as living?

It is theorized that a single cell is difficult to survive under natural condition without being self-gravitationally anchored or attaining steady state condition or under multi-assembled single cell condition. A single cell cannot survive in isolated way, unless it is anchored by inertia. A minimal inertial mass is required for survival.  In plant tissue culture, unless a callus (“explants”) of say above 500 mg40 or suspension of cultures of say, 3-4 cubic centimeter (in terms of PCV - packed cell volume) is used, it is difficult to maintain continuity of life and growth from individual cells. Similarly in the final volume for cell culture, maintaining cell density as low as 3 x 105 to high of more than 10–15x 106 cells/ml of inoculums are required. Why a minimum mass is required for cell culture under multi-assembled single cell condition. Is it for anchorage? There is a literary proverb that “A Rolling stone gathers no moss”. This is not only a literary proverb but based on scientific observation and fact of the commoners.

As biomass possesses both gravity and inertia, it has the characteristic that it can act as anchor as if entire biomass is concentrated at the centre or at the equilibrium point. Thus after seclusion, unless a biomass is anchored or pivoted in a steady state condition through the action of inertia, attainment of accelerated condition would be difficult. This is similar to frictional force (force resisting the relative motion of two surfaces in contact) between feet and ground in steady state condition required for smooth walking. Mitochondria, a primary energy producer in the cell, constantly change shape, i.e. it remains in motion. Electron transport chain would be away from central core of a self gravitating cell, as the intensity of gravitational energy gets reduced from the core to the periphery when it can be overpowered by electrostatic force (Illustration 17). Therefore we can propose that critical quantity of biomass is important for acting as inertia upon which mechanism of self gravity can operate i.e. further growth is possible on anchorage.

15. Energy producing organelles or sites located away from the centre

Normally carbohydrate is considered as main source of energy for biological mass. One gram of carbohydrate on oxidation in the body during respiration gives about 17000 joules of energy, whereas 1 gram of fat gives about 37000 joules of energy. ATP is produced through four basic methods: in bacterial cell walls, in the cytoplasm by photosynthesis, in chloroplasts, and in mitochondria. However, energy producing organelles or sites is located generally away from the centre of self gravity of a cell or away from the central axis of the biomass in a reference frame at that point of time (Illustration 18).

16. Some anomalous hypothecations in health science

We have noticed some anomalous hypothecation in health science on describing mass or weight viz. in describing Body Mass Index (BMI), Body Surface Area (BSA). Basal Metabolic Rate (BMR), Resting Metabolic Rate (RMR); Physical Activity Level (PAL), Lean Body Mass (LBM) are the most popular answered phenomena in life science.  These are explained in details below with the invitation for formulating correct hypothecation in the light of self gravitation bio.

17.  Body Mass Index (BMI)

Body Mass Index (BMI) or Quetelet index 41, remains a controversial statistical measurement of health. Body mass index is defined as the individual's body weight divided by the square of his or her height. {BMI= Weight (kg)/ height2 (m2)}. The WHO regards a BMI of less than 18.5 as underweight and may indicate malnutrition, or other health problems, while a BMI greater than 25 is considered overweight and above 30 is considered obese42. BMI determine risk of developing heart disease and other health problems such as diabetes. BMI

As per ‘Self Gravitation Bio’, BMI is nothing but weight/ height or mass/volume = density of the body mass. It gives indication for quantum of self gravitational attraction, as density of the mass is important determinant for gravitational potential energy. Age, an influencing factor of BMI, could be taken as the capacity to generate metabolic kinetic energy. Other influential factors include gender and accumulation of fat (adipose tissue) in individual body is primarily a reflection of differences in body mass and density. Once presence of self gravity is resolved in individual body, other factors can automatically be laid to rest on meticulous study in right perspective.

18.  Body Surface Area (BSA)

Weight can be a measure for gravitational force over a mass. It cannot be a measure for ‘surface area’.   But in calculating Body Surface Area (BSA), health specialist has to take into account of the total gravitation force with incorrect nomenclature as ‘surface area’ as reflected in equations from (4) to (9) below. Let us see how and why it happens. Body Surface Area (BSA) is used to measure renal function- glomerular filtration rate (GFR), to calculate cardiac index (cardiac output/BSA), Chemotherapy & Glucocorticoid dosing. Body surface area (BSA) is considered "normal”- 1.7 m², average (men) 1.9 m², (women) 1.6 m²; child (9 years): 1.07 m², (10 years) 1.14 m²; (12-13 years): 1.33 m²; neonate: 0.25; 2 year: 0.5 m2.

But BSA remains controversial starting in 1916 with the Dubois & Dubois formula 43,  (Illustration 49 Equation 5)

A commonly used formula is the Mosteller formula 44, published in 1987: (area in sq m from weight in kg and height in cm): (Illustration 49 Equation 6)

Haycock formula (in children) 45: (Illustration 49 Equation 7)

Gehan & George formula46 (Illustration 49 Equation 8)

Boyd's formula47: (Illustration 49 Equation 9)

National Cancer Institute (Illustration 49 Equation 10)

From the above, it is clear that there should be a correction in our concept on body surface area with self gravitation bio.

19. Basal Metabolic Rate (BMR)

Basal metabolic rate (BMR) remains controversial for long with no satisfactory solution at sight within existing principles. BMR is considered as the amount of energy expended while at rest in a neutrally temperate environment, in the post-absorptive state (meaning that the digestive system is inactive, which requires about twelve hours of fasting in humans). The release of energy in this state is sufficient only for the functioning of the vital organs, such as the heart, lungs, brain and the rest of the nervous system, liver, kidneys, sex organs, muscles and skin. BMR decreases with age and with the loss of lean body mass. Increased muscle mass can increase BMR. Aerobic fitness level, a product of cardiovascular exercise, while previously thought to have effect on basal or resting metabolic rate (RMR), has been shown in the 1990s not to correlate with BMR. BMR is measured under very restrictive circumstances when a person is awake, but at complete rest. An accurate BMR measurement requires that the person's sympathetic nervous system not to be stimulated.

In fact, in absence of proper viewing perspective over the definition of ‘mass’, as measure of gravitational force, calculation of metabolic rate remains controversial from 1880 till date.  Max Rubner (1880)48 reported that mammalian BMR is proportional to Mass 2/3. Kleiber (1932)49 supported by Brody (1945)50 modified proportionality to Mass ¾. Several other prediction equations also came into being. Historically most notable was Harris-Benedict equation51, which was created in 1919:

for men, (Illustration 49 Equation 11a)               & nbsp;     

for women, (Illustration 49 Equation 11b)

where P is total heat production at complete rest, m is the weight, h is the stature (height), and a is the age, and with the difference in BMR for men and women being mainly due to differences in body weight. In fact, we are of the opinion that mechano-structural difference between genital organs of men and women primarily lies mostly with the extrovert and introvert expression respectively of the soft matter during the formative stage, on which we are constrained to elaborate at present except requesting for detailed mechanical analysis on four dimensional structural features of men and women. However for purpose of estimation of BMR, Harris-Benedict equationwas the best prediction equation until recently, when MD Mifflin and ST St Jeor in 199052 created new equation: (Illustration 49 Equation 12)

where s is +5 for males and −161 for female.

BMR was also attempted to be correlated with change in life style. It was stated that during the last 100 years, lifestyles have changed.  A survey in 2005 53 showed that it is about 5% more accurate. These formulae are based on body weight, which does not take into account the difference in metabolic activity between lean body mass and body fat. A more accurate formula is the Katch-McArdle formula54 based on lean body mass: (Illustration 49 Equation 13)

where LBM is the lean body mass in kg.

In the mean time other issues goes on hunting life science researchers. In both endothermic and ectothermic animals, the normal metabolic rate is inversely related to body size; the smaller the organism, the higher the relative metabolic rate. While dealing endothermic and ectothermic animals, naturally temperature has been brought into the scenario. But here also what is true for endotherms is not applicable for ectotherms. For instance, temperature is considered as an important factor in enzyme activity. It is speculated that as the temperature increases up to about 40oC, the velocity of an enzyme-catalyzed reaction increases because the substrates collide with active sites more frequently as the molecules move more rapidly due to thermal agitation55. Because the metabolic reactions are enzyme catalyzed, metabolic rate would be proportional to temperature, up to the point where the enzyme is denatured. The relationship between metabolic rate and temperature is often expressed as Q10, which measures the rate increase for each 10o rise in temperature. It is contemplated that the abrupt decline above 40o represents the point at which the weak bonds that hold enzymes in their specific active conformations begin to break. As a result the enzymes become denatured and metabolic activity is severely disrupted.  Enzyme is a class of protein. We have dealt protein denaturation with rise in temperature and its relation with self gravity subsequently.

Inverse relationship between metabolic rate and body size was said to be easily understood in the case of endotherms; stating that smaller animals have a greater surface-to-volume ratio, and consequently a larger relative heat loss to the environment per unit time55. To maintain a constant high body temperature despite rapid heat loss across a body surface, a small animal ought to oxidize food at a high rate. Because the relative amount of food consumed and the pace of digestion, respiration, and so on must rise with decreasing body size, there is a lower limit on the size of endotherms. The smallest mammals weighing only about 4 grams are required to eat nearly their own body weight of food every day, and can starve to death in just a few hours if deprived of food.

In case of ectothermic animals, the same principle does not hold. Ectotherms lose their metabolic heat to the environment and do not normally respond to heat loss by increased metabolism, so larger size and its concomitant smaller surface-to-volume ratio should actually retard heat loss somewhat, and the conserved heat ought then to speed up metabolism. It is thought that increasing size involves a disproportionate increase in the mass of skeletal and other connective tissue in animals—an alligator, for instance, requires more inactive support structure than a salamander. Since these tissues are relatively inactive metabolically, the average metabolic rate per unit weight for the organism as a whole may fall as the proportion of these less active but necessary structural tissues rises55.

Larger animals have relatively slower metabolisms than small ones. A mouse must eat about a third of its body mass every day not to starve whereas a human can survive only on 2%. The relationship follows a power law: basal metabolic rate (R) is proportional to the ¾ power of an animal's mass (M). This relationship, the Kleiber Law49, 50, can be drawn as a straight line on a log-log plot (Illustration 19). Mysteriously, this simple relationship holds, from simple organisms to most complex ones, from microbes to giant blue whales across 18 orders of magnitude in body mass55.

To arrive at conclusion, some ambitious researchers56 proposed a concept based on analysis of circulatory system to explain how characteristics like body size and energy consumption differ from species to species along fixed scales. Their scaling was based on some small to huge animal to demonstrate mathematical and geometric nature of networks that distribute nutrients and carry away waste and heat. The bigger the animal, more efficient it uses energy (Illustration 20). Unfortunately such mathematical and geometrical scaling concept also seems did not work in greater context of family for living organisms. 

Barbara Fischer of the theoretical population ecology and evolution group, Biology Dept., Lund University57 however stressed on a unifying principle of ecology with the ‘metabolic theory of ecology’. It states that metabolism provides the fundamental constraints by which ecological processes are governed. It suggests that from single organism’s life-history strategies to population dynamics and ecosystem processes at all levels of organization could possibly be explained in terms of constraints imposed by metabolic rate.

Now question arises, who could impose so called ‘constraints’ over metabolic rate? Universally gravity is the known ‘culprit’ (?) which often put constraints in our activities. As stated above, mass and metabolic rate is inversely related. That is, ‘mass’ or in other term ‘gravity’ itself might not allow metabolic energy to act in unlimited manner. In one hand, part of mass (say 2/3 to ¾ or 66 to75%) is expended towards maintaining metabolic rate. On other hand, we know that 100 percent of the same mass works towards generating self gravitational potential energy. There is thus a huge difference between kinetic (metabolic) and potential (gravitational) energies. We are fortunate to say that inertia of gravitational potential energy plays a leveling ground for balancing gravity’s compressive role on putting limitation. The metabolic energy is thus on a tug-of-war between potential and its own kinetic energy.  When force of gravity and inertia are balanced there will be no change of motion. With such balanced force, motion of the object remains stationary i.e. net force is zero. When metabolic energy is put at the rate of 10-12 to 10-6 kcal/hr, it can move unicellular organisms. It would have to work against both intrinsic and extrinsic gravity (if not remains in secluded condition). Similarly cold blooded animals can be in motion against self gravity and planetary gravity, when metabolic rate is 10-8 to about 100 kcal/hr. Warm blooded animals do the same work with metabolic rate having less than 100 to 103 kcal/hr. Under secluded condition, some exception may occur when due to upward force of fluid, the animal would require less energy compared to energy requirement of same mass in land. Thus presence of metabolic energy can be felt taking into account both intrinsic and extrinsic ‘gravitational force’ with resting metabolic rate (RMR) for meeting most of the demands on working against self gravity where as physical activity level (PAL) could be mostly to meet demands for working against extrinsic gravitational force. This will be clear from the under mentioned discussions.

Take an example on movement of human thoracic diaphragm. We will discuss subsequently the origin of its dome shape arc structure, the issue of maintaining constant angle between radius from the common centre and tangents (over intercepted arc). Here potential energy of self gravity contracts its dome shape structure. The inertia attempts to bring back contracting surface to original position. Kinetic energy of metabolism works against it, thereby, allowing the dome shape structure to relax. Unbalanced forces causes change in motion in a curved surface in speeding up and slowing down (Illustration 21). Resting metabolic rate (RMR) is therefore primarily involved in such internal activity against self gravity.

On the other hand, raising a ball through a height above earth’s surface by hand involves metabolic kinetic energy against potential energy of earth’s gravity and invites spending metabolic energy as per physical activity level (PAL) on contracting and relaxing muscles (Illustration 22).

Thus understanding distribution of metabolic energy to work against self gravity and planetary gravity, role of potential and kinetic energy including inertia is a major gap area of investigation in life science.  It would not only clear all ambiguity towards basal metabolic rate (BMR) but also serve as a precursor of various new researches in biological science including health of human, animal, plant and microbes. 

Centre of self Gravity

20. Why central position is vital?

The central position in a gravitating system would be as if the entire mass in the sphere of influence would have been concentrated at that point, a distinguishable features of gravitational force from other basic forces viz. electromagnetic forces or any other local forces like surface tension, elastic forces etc. (Illustration 23) .

21.  Why nucleoid, nucleolis or nucleus tend to remain in central position?

Why nucleoid in prokaryote and nucleolis or nucleus in eukaryote, all which are made of swarm of macromolecules and little denser in the spatial distribution than the surrounding cytoplasmic matrix, attempt to remain in central position of the cell? (Illustration 24)

22. Generation of ‘muscle tone’ remains elusive in human physiology

Muscle tone or background tensions remain elusive in human physiology. In the book “Fundamentals of Neurophysiology” Robert F. Schmidt pointed out that “Summation of the twitches of many fibers, excited asynchronously at low frequencies up to 5/second, generates a total force that does not fluctuate very much, with amplitude that must be approximately proportional to the average frequency of excitation. The ‘background’ tension produced in this way by summation of the twitches of many fibers is called tone. All the muscles in a living organism possess such tone. Even in a relaxed limb, the motor nerves are activated at low frequency.”  Gray’s Anatomy empirically denies existence of muscle tone, as it doesn’t show up on an electromyography. But Gray’s anatomy admitted that an electromyograph can’t pick up low level, steady-state action unless the motor units immediately adjacent to the contact are firing. It just reads as background noise. Other authors postulate that there is an inherent elasticity in the muscles, and still others talk about muscle tone but don’t have a clear picture of what it is. Interestingly no one denies existence of static and balanced. It is stated that tone works 24 hours a day.  What force would make it functional continuously?  The nerve impulse is primarily an electrical event. Each neuron is like a tiny biological battery ready to be discharged. It requires to be charged constantly. As life process starts with accumulation of mass, upon which force of gravity naturally works for 24 hours without any external inputs. Can it be responsible for subtle tone in a body? Let us examine the issue in little details.

23.  ‘Build-up’ & ‘break-down’ mechanisms in living mass

There are two inverse-square central forces such as the gravitational or electrostatic potential. Gravitational fields have the same range as electromagnetic fields. The gravitational field is much weaker than the electromagnetic field. The positive and negative charges of the electromagnetic field tend to compensate each other's fields. But masses are not compensated for which gravitational force cannot be compensated. However notice to gravitational force gets evaded. But when there could be a difference in the quantity of mass within a span of time, manifestation in the variation of gravitational binding energy58 according to gravitational mass would be spectacular. Let us note that non-living objects have got no ‘build-up’ and ‘break-down’ mechanisms of carbohydrates in mass. It is static mass. In living objects, on the other hand, there is change of mass through ‘build-up’ and ‘break-down’ mechanism of carbohydrates59. It is a unique character that operates in regular manner in all living objects.  Photosynthesis and respiration are two alternate processes in plants wherein photosynthesis means gain (‘build-up’) in biomass whereas carbohydrates expended during respiration and growth is loss (‘break-down’) of mass per unit area. Adenosine 5′-triphosphate (ATP) plays a central role in ‘build-up’ and ‘break-down’ mechanism process of mass in all living organisms. Thus it can be seen that in non-living matter, mass remains constant whereas in living matters quantity of mass in the form body weight and composition (density) gets changed with the changes in the state of energy in the form of biochemical products and with the gain or release of temperature.

24.  Spectacular action of self gravity in muscle tone while living and not when dead

Now let us see what would happen if there is loss and gain in living mass along with time in a self gravitating environment. The change in mass in a membrane bound self gravitating close structured living objects would cause change in gravitational binding energy resulting into a source of potential energy as well as inertia. Metabolic energy primarily acts as source of kinetic energy. This would create a tension within the mass say, in the muscles fibers, vessels etc. making these lengthened followed by shortened, or tight followed by loose, or stretched followed by slack, or firm followed by flaccid, rigid or tautness followed by flexible and so on, as per location and structural anatomy of the particular vessel or muscle. This alternate movement might manifest as beats, or excited asynchronously at low frequencies in addition to increase or decrease in potential gravitational compression and kinetic relaxation energy due to inertia plus metabolic energy. Such variation in the internal pressure due to variation in potential and kinetic energy might be the source of power for giving non-neural background tension or tone to the body. However this would be an interesting area of research for biophysicists.

25.  There is no complete loss of tone during paralysis

Let us cite few examples below to show how generation of muscle tone or background tension remains an elusive till date.  Paralysis is the loss or impairment of motor function in a part due to a lesion of the neural or muscular mechanism.  Paralysis is most often caused by damage in the nervous system, especially the spinal cord. It takes about one-thousandth of a second for a neuron to fire an impulse and return to its resting level. Both sympathetic and parasympathetic neurons have a constant rate of firing under normal conditions. This is also called their "tone", but of neural origin.  It maintains the normal rate of heartbeat, keeps blood pressure within a normal range and maintain homeostasis.  Of course, the sympathetic and parasympathetic firing rate changes greatly during fight-or-flight responses. Paralyzed muscle may be flaccid, flabby, and without appreciable tone, or it may be spastic, tight, and with abnormally high tone that increases when the muscle is moved. But most interesting fact is that there is no complete loss of background tone during paralysis. Complete loss of tone is only available with death.

26.  Tone is lost after death during pallor mortis and not while living

As per Law of Laplac60, (Illustration 49 Equation 14)

where T= ‘wall tension’, p = pressure, r = radius, t = wall thickness. For a given pressure, increased radius requires increased wall thickness to accommodate a stable ‘wall tension’; also, increased pressure requires increased thickness to maintain a stable ‘wall tension’. The Law of Laplace explains various phenomena encountered in the pathology of vascular or gastrointestinal walls. The ‘wall tension’ is said to represent the muscular tension on the wall of the vessel. But how far it is true? Who controls the ‘wall tension’ is not yet meticulously studied taking into account the presence of self gravity.  Break down of ‘wall tension’ is conspicuous only after death. We will discuss the issue in subsequent paragraphs.

Generally the tone is said to be ‘regulated’ (decreased or increased) by virtue of sympathetic and parasympathetic supply. The autonomic nervous system (ANS) operates without conscious control, relying upon reflex arcs that are dependent upon hypothalamus and medulla for overriding control. Autonomic nerve fibers innervate cardiac muscle, smooth muscle, and glands. Through these fibers the ANS said to play a role in regulating blood pressure and flow, gastrointestinal movements and secretions, body temperature, bronchial dilation, blood glucose levels, metabolism, micturition and defecation,  pupillary light and accommodation reflexes, and glandular secretions, just to name a few. A mechanical engineer will however view in different angle to unearth the word ‘regulation’.

For instance, geared elevator system (lift) works on a number of engineering principles. Electric motor turns the gear that rotates the sheave. A sheave is just a pulley with grooves around the circumference.  Sheave grips the hoist ropes which are connected to counterweight (Illustration 25 left). It is therefore technically wrong to say, elevator is regulated by electrical force. It only regulates gear. Similarly it is incorrect to say that nervous system regulates various human physical activities. Electrostatic nervous system cannot have ‘load’ or ‘weight’ bearing capacity. It can at best act as trigger to propel a part of the mechanical system for lifting of load. It is therefore advisable to understand the mechanical system as a whole to ascertain ‘cause-effect’ relations in life science in better manner. Correspondingly a rescuer can easily drag a drowning person in water by holding his hair or bathing suit. But same thing is not possible in terrestrial environment (Illustration 25 right). Reason is obvious.

Now let us return back to our original contention.  Within minutes of the heart stopping, a process called pallor mortis61, blood drains from the smaller veins in the skin. That is its original background tone is lost. Therefore question arises why tone is lost after heart-beating death62, 63 during pallor mortis and not while living? Why nerve impulse fails to act when clinically dead. Loss of tone is related to potential and kinetic energy of mass. This small difference in the pathology of paralysis and death needs thorough investigation.

27.  Intrinsic muscle tone is constantly maintained when living but loose after death

We see that intrinsic muscle tone is maintained for 24 hours when living. After death, intrinsic muscle tone is lost. For example, due to the tone in the longitudinal muscle bundles in the gut, the length of the small intestine remains at half while living. After death gut length becomes double, say about 24 ft. During paralysis such an event is rare. At the moment of death, all of the muscles in the body relax, a state called primary flaccidity. Eyelids lose their tension, the pupils dilate, the jaw might fall open, and the body's joints and limbs are flexible. With the loss of tension in the muscles, the skin will sag, which can cause prominent joints and bones in the body, such as the jaw or hips, to become pronounced.

28. Edema occurs in lowers or dependant parts of the body after death

After 2 to 6 hours of death, external gravity begins to pull blood to the areas of the body closest to the ground, a process called livor mortis. Hypostasis or settling of blood and the dependent edema i.e. fluids in lower or dependent parts of an organ or body occurs after death. Why downward pull towards external direction? Why such severe manifestation of earth’s gravity is not pronounced while living? In fact while living, full tone could be maintained when there is a balance between potential energy of self gravity and kinetic energy of metabolism within self gravitating environment. But with loss of such equilibrium, extrinsic (earth’s) gravity could pull down fluids, blood in the direction of stronger external gravity, as described above and the organism behaves as inert on losing its tone (Illustration 26).

29. Intuitive model on generation of ‘background tone’

Muscle tone64 is usually defined as the amount of contraction in a resting muscle. It is a static, balanced, isometric contraction between agonist and antagonist (both internal forces) in every muscle in the body. It never lets go completely, even in sleep, when all dynamic muscle activity is gone. It operates when one does nothing. Muscle-building exercise elevates tone, can even slam it up considerably, but at whatever level the involvement of contraction, tone still remains static and constant at any given time.  

It is argued that between cardiac and flat muscles, flat muscles resist becoming hypertonic. They can’t squeeze off their veins so they can’t encapsulate lactic acid. Cardiac muscle is non-spastic because it can burn lactic acid.  However exhalation and inhalation mechanism is based on thin dome-shaped sheet of muscle of the thoracic diaphragm which is said to be controlled by phrenic nerve. It is to be remembered that electrostatic nervous system can regulate physiological process but when the question of bearing certain ‘load’, its controlling role would be limited. Therefore unless a mechanism similar to pneumatic system operates, simple nerve impulse cannot control movement of load. This is a gross oversight in life science.

Thoracic diaphragm is kidney shaped in outline and has the ability to contract from its edges towards its centre. Its centre lies horizontally across the body dividing the trunk into two compartments: the thorax (the chest) and the abdomen (the belly). The thorax contains the heart and lungs while the abdomen contains the organs of digestion. Geometrically dome shaped structure is an intercepted arc, centre point of which is coinciding somewhere in the imaginary centre of self gravity as per human architecture. Potential energy (compressive) of self gravity contracts the dome shape structure. Kinetic energy decompresses, thereby allowing the dome shape structure to relax. While undertaking both contracting and relaxed condition, it is maintaining a constant angle between radius from the common centre and tangents (from intercepted arc), as shown in left side of the illustration (Illustration 27).  Similarly, if tangents are drawn on the circumference (intercepted arc) of the balloon like inflated heart, these will also form constant angles with the radius from the centre of the structure during embryonic stage65. The alternate ‘half-bulging’ structure in the muscles is available around skeleton in the periphery on one side of a joint and end via a tendon or ligament on another side of the joint, functioned by sympathetic and parasympathetic nerves. If tangents are drawn over such alternate ‘half-bulging’ intercepted arc, there also constant angles can be seen between tangent and radius drawn from central position, as shown in the middle of the illustration (Illustration 27).  Thus it is apparent that the basic geometrical structure of different organs/ mechanisms in human coincides with the centre and related features of potential energy of self gravity (U = mgh) and kinetic energy (Ek = ½ mv2) against it. Manifestation of background low frequency ‘muscle tone’ is the interaction between self gravitational binding (potential) energy and metabolic (kinetic) energy against potential energy. Hence self gravitational potential energy balance66, 67 needs to be worked out in human axisymmetric con?guration structured under stratified density of soft matter or fluids where viscous forces may play to create divergent geometry at early stage of formation. 

Under equilibrium condition between potential and kinetic energy, muscle tone would remain static and balanced from centre to periphery. Under non-equilibrium condition, especially due to disproportionate build-up of mass, self gravitational tone or background tension would increase from periphery to the centre, leading to various collapse in living mechanism. The close relation between obesity and cardiometabolic syndrome 68, 69 may be cited as an example. Thus we find that “balance is the law of life”, though we are to move with unbalanced potential energy with the kinetic energy. 

30.  Abundance of logarithmic spiral in nature vis-à-vis self gravitating phenomena

It is interesting to note that gravitational waves works like water, sound and electromagnetic waves and is able to carry energy, momentum, and angular momentum from their sources. Very low frequency waves may be impossible to detect but it seems that there is some indirect evidence for its existence. For instance logarithmic spiral70 is also known as the growth spiral, equiangular spiral or spira mirabilis. The length of the radius goes on increasing with the shell.  The logarithmic spiral has the unique property of maintaining a constant angle between the radius and the tangent at any point on the curve (Illustration 28). This spiral is related to Fibonacci numbers, golden ratio, or golden spiral in snails, snakes and others. Unless mechanism of potential energy of self gravity versus kinetic energy of metabolism is not brought into the scenario, formation of logarithmic spirals in nature will continue to remain elusive.

31.  Human average body frequency

Various persons viz. Bruce Tainio, Dr. Royal R. Rife, Nikola Tesla, Dr. Robert O. Becker had stated to have built frequency generator, frequency monitor and claimed71 to have found that in a healthy body average frequency is 62-72 Hz . When the frequency drops, the immune system is said to be compromised. We do not like to comment in favor or against such claim. Rather we suggest that under strict scientific procedure a thorough investigation could be made. Earlier people were conversant with the frequencies of the electrical and magnetic forces. So their analyses were reflected in their thinking. Now when there is a possibility of generating frequency due to inward breakdown and outward buildup mechanisms with the force of self gravity, the matter may be reinvestigated. It is to remember that angular velocity, angular frequency and hertz all have the dimensions of 1/s, angular velocity and angular frequency are not expressed in hertz, but rather in an appropriate angular unit such as radians per second. Thus a disc rotating at 60 revolutions per minute (rpm) is said to be rotating at either 2π rad/s or 1 Hz, where the former measures the angular velocity and the latter reflects the number of complete revolutions per second. The conversion between a frequency f measured in hertz and an angular velocity ω measured in radians per second are (Illustration 49 Equation 15):

Similarly higher frequencies of the quantum-mechanical wave functions of high-energy are expressed in terms of equivalent quantum energy, which is proportional to the frequency by the factor of Planck's constant. Can we therefore think that low and high frequency could possibly be a differential feature between self gravitational waves and electrical waves? (Illustration 29) Thus there is ample opportunity to detect the frequency of gravitational waves at mesoscopic length scale on the principle of equivalence in tune with macroscopic and microscopic scales.

32.  Body cools down on death after loss of contraction-relaxation of self gravity

After death, the human body begins to cool down from its normal temperature of 37° Celsius until reaching the ambient temperature around it. Known as algor mortis, the decrease in body temperature follows a somewhat linear progression. Decrease in body temperature is two degrees Celsius in the first hour; one degree each hour thereafter.  Let us see how this situation can happen? In a self gravitating environment, on collusion between random molecules due contraction and relaxation mechanism through alternate ‘build-up’ and ‘break-down’ processes of mass, body temperature gets elevated. But when self gravity loses such contraction and relaxation process, the speed of corresponding molecules gets slower with loss of mobility and resistance, resulting in fall in body temperature with death. Thus loss of mechanism of self gravity means motion of molecules gets rest and random motion of molecules that endows with the property of temperature gets die down. During neural-regulated paralysis, temporary or permanent, there is no such spectacular fall in body temperature. The fall in body temperature is spectacular only after self gravity loses its strength and gets mingled with external gravity of the earth. Unless the mechanism of self gravity is not brought into the life science scenario, rise and fall in body temperature of living organisms will remain elusive.

33.  Which force regulates stretching and relaxation during esophageal peristalsis?

An interesting study on the effect of earth’s gravity on esophageal peristalsis in humans was studied72. Many mammalian species including non-human primates consume water in a body position not aided by earth’s gravity and it has been conjectured that esophageal peristalsis overcomes earth’s gravity in humans. Let us then examine the peristaltic phenomena in the light of self gravity. The esophageal wall is composed of distinct layers- outer longitudinal muscles and inner circular muscles. The function of outer longitudinally oriented muscle layer is yet unclear72, but it is stated to be involved in inner mucosal movement. Sequential contraction of longitudinal muscle occurs during peristalsis. This is stated to serve in order to shorten the esophagus and increase the cross-sectional diameter, thereby facilitating bolus transport. William G. Paterson73 while reviewing the whole process pointed out that much remains to be learned about the physiologic control of esophageal peristalsis. At rest it may contract in a cyclical pattern. Intracellular recordings have revealed rhythmic depolarization-repolarization with a frequency of 2 to 3/min. The duration of contraction also appears to vary along the esophagus. Contraction is longer distally (away from the center of the body) than proximally (nearer to the center of the body). The peristaltic velocity averages about 3 cm/sec in the upper esophagus, then accelerates to about 5 cm/sec in the mid-esophagus, and slows again to approximately 2.5 cm/sec distally. Why such positional variation e.g. rapid in proximally and slower in distal?  Unless self gravity which is stronger at centre and weaker at periphery or at distal points is not brought into the scenario, it will remain elusive in spite of presence of myenteric plexus over the whole gut.

The primary origin of push-pull travel force with alternate stretching and compression from the peripheral to central direction can be apparently seen in foetus position (Illustration 30). Compression and resultant stretched force due to inertia and action of the self gravity is apparently available from mouth to stomach, considering a point somewhere around stomach as the central position and mouth as well as anus as in the periphery of the self gravitating body. Centre being higher compressive zone, peristaltic velocity will be higher proximally than the periphery. Thus origin of the peristaltic movement for longitudinal muscle with push-pull travel force can become clear with the introduction of self gravity.  However this is a gap area of investigation.

34.  What causes channel narrowed or dilated during trafficking?

There are many instances of constriction and dilation in channel movements in trafficking in both animals and plants. But in most of the cases these are in half way to give a complete understanding. In the plant cell wall, for instance, plasmodesmata are channels that in conjunction with associated phloem form an intercellular communication network that supports the cell-to-cell and long-distance trafficking of a wide spectrum of endogenous proteins and ribonucleoprotein complexes. The narrowed and dilated route of trafficking of such macromolecules is of importance in the orchestration of non-cell autonomous developmental and physiological processes. Plant viruses encode movement proteins that subvert this communication network to facilitate the spread of infection74. Macromolecules move according to electrochemical gradient and hydrodynamic (Stokes) radius. Plasmodesmata and more specifically constriction and openness of desmotubule in mesophyll cells of plants is regarded yet an unknown function.(Illustration 31) Which space-time bound pressure control hydrodynamic radius at various strategic locations? This is a gap area of investigation in the light of self gravitating environment.

35.  Why nuclear-cytoplasmic ratio is important for health?

Hypotonic, isotonic and hypertonic solutions are used for making cell turgid, flaccid and plasmolyzed respectively on adjusting its volume.  Therefore volume regulation is important and vital in cellular response under aqueous media. Tonicity of aqueous solutions (water with solutes, such as salt, dissolved in it) is based on cellular responses to that solution. Solutions are hypotonic if the cells or tissue swell in response to immersion. Solutions are isotonic if the cells or tissue neither shrinks nor swells in response to immersion in that solution. Solutions are hypertonic if the cells or tissue shrink in response to immersion.  Why volume regulations in the overall passage route and in the overall size of the inner macromolecule are important?  Why any physical imbalances between the two as regards their sizes create health hazards? Control of sizes of inner macromolecules may be hydrodynamic based on tonicity (Illustration 32), but what about overall size of the trafficking route? Which factor control size of the trafficking route? This is a gap area of investigation.

The nuclear-cytoplasmic ratio is a ratio of the size (i.e., volume) of the nucleus of a cell to the size of the cytoplasm of that cell. The nuclear-cytoplasmic ratio indicates maturity of a cell, because as a cell matures the size of its nucleus generally decreases.  Why size of the nucleus should decrease with maturity? The phenomena can better be answered with the concept of self gravity. Self gravitational pressure acting inwards thought to be exerted on the surface outside.  Thus it could squeeze fluids and gas out of the surface. Such squeezing action would be maximum at the nucleus, as if a core segment in a self gravitating body. Maturity means an increase in mass with increase in density. More the mass with increase in density more would be the squeezing action, as per classical gravitational law. Ratio is fairly constant for a particular cell type. 

An increased nuclear-cytoplasmic ratio is commonly associated with precancerous dysplasia as well as with malignant cells. For example, "blast" forms of erythrocytes, leukocytes, and mega karyocytes start with an N:C ratio of 4:1, which decreases as they mature to 2:1 or even 1:1 (with exceptions for mature thrombocytes and erythrocytes, which are anuclear cells, and mature lymphocytes, which only decrease to a 3:1 ratio and often retain the original 4:1 ratio)75.  On correcting cytoplsmic density with addition of hypertonic, isotonic or isotonic normal saline thus regulate nuclear cytoplasmic ratio. For instance, tumor cell morphology was visualised76 through use of transmission electron microscopy following 1 hour exposure to a hypertonic environment. The cells in a hypertonic environment exhibited a reduction in nuclear/cytoplasmic ratio, well defined plasma membranes and contained intact organelles with no evidence of nuclear condensation or apoptotic bodies (Illustration 33). This is indicative that buoyed up force of the fluid can be manipulated within the stipulated volume of the cell to get desired size of the nucleus, through process of osmosis and diffusion. 

36.  Matching inward wall pressure in cellular activity vis-à-vis self gravity

Turgor Pressure is the support for plants generated by wall pressures. Water enters the cell by osmosis from the higher osmotic potential (solute potential) to the lower osmotic potential. The volume of the cell cytoplasm increases forcing the plasma membrane outwards against the cell wall. A pressure develops called the turgor pressure (pressure potential), which is excerpted against the cell wall. The outward pressure is matched by an inward pressure, equal in magnitude but opposite in direction. These pressures are called turgor pressures and provide mechanical support to the plant tissue. If a plant experiences a lack of water the cell becomes plasmolysed, wall pressure is lost and the plant wilts. Normally the outer surface is amenable to matching inward pressure of inertia (Illustration 34). But there are many circumstantial evidences when matching inward wall pressure could get supplemented by some extra forces which affect cellular activity. For instance, turgid pressure in plant cell gets modified on maturity with decrease in vacuole size (free space) and increase in mass of cytoplasm per unit volume, as shown in Illustration 35, which causes more than usual inward pressure resulting in narrowing of flow passage. Such a situation can be explained for increase in pressure of self gravitation with increase in mass per unit volume with age. However this is a gap area of investigation.

37.  Mechanical loads and centrosome - microtubule organization

Gravitational potential energy is inward and kinetic energy is outward against binding energy. Mechanical living cell deformation studies have demonstrated that mechanical loads are borne by microtubules, which are balanced by tensile forces in contractile elements of the cytoskeleton77. Moreover, the disruption of microtubules yields a transfer of forces to the extracellular matrix, a decrease in cell stiffness and altered cell shape. Evidence also suggests that similar forces that are active on micro-tubules are integral to the maintenance of nuclear shape and also proposes that the transfer of mechanical stress across the cytoskeleton may link the alterations in cell and nuclear shape that occur during cell spreading and retraction78, 79. It is interesting to note that in animal cells, the major microtubule-organizing center is the centrosome, which is located adjacent to the nucleus near the center of interphase (non-dividing) cells. During mitosis, microtubules extend outward from duplicated centrosomes to form the mitotic spindle, which is responsible for the separation and distribution of chromosomes to daughter cells. The centrosome thus plays a key role in determining the intracellular organization of microtubules, although most details of its function remain a mystery. Thus between centrosome and microtubule organization, it can be seen that microtubules in most cells extend outward from a microtubule-organizing center, in which the minus ends of microtubules are anchored. It is apparent that the formation of centrosome is primarily influenced by potential energy of the self gravity, whereas microtubule organization is influenced by kinetic energy. 

Centralized arrangement of microtubules under inverted colour of the photograph taken on using green fluorescent protein (GFP) tagged proteins by Jeremy Simpson and Rainer Pepperkok80 are presented in Illustration 35. Picture demonstrates conclusively the operation of invisible binding energy of self gravity and kinetic energy working against the binding energy in living cell.

Of late a very interesting question “What determines cell size?”- was sought be answered by group of independent researchers81. In the forum article “Physical limits of cell size for embryonic cell division in Caenorhabditis elegans”, Akatsuki Kimura pointed out that in transparent C. elegans embryos, centrosomes have the ability to position themselves at the cell center, enabling the mitotic spindle to position at the cell center (Illustration 36). The mechanisms mediating centrosome centration may differ among species. Recent studies have supported the idea that the cytoplasmic pulling force is a major driving force for centrosome centration in animal cells. Microtubule-dependent centration of the centrosome must be facilitated by microtubules, which grow from the centrosome and span throughout the cytoplasm to find the geometrical center of the region. Cell size may be limited by the physical properties of the cell and positioning of the mitotic spindle at the cell center is critical for symmetric cell division. Nothing happens without a cause. Potential energy of the self gravity binds and kinetic energy works against it. Hence there is need to study invisible central tendency of the force of self gravity and effect of mutual gravity of two interacting masses. 

38.  Inner cell mass (ICM) influences potency in stem cells?

Stem cell potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell. It can be totipotent, pluripotent, Multipotent, Oligopotent, Unipotent etc. as per their characteristics for regeneration or differentiation.  Most interesting fact is that inner cell mass (ICM) influences potency in stem cells. For instance, pluripotent, embryonic stem cells originate in inner cell mass (ICM) cells within a blastocyst82. Why inner cell mass or central position is an important location as non-potency stage for regeneration or differentiation in stem cells? Compared to periphery, attractive gravitational pull/ force towards core or central position are higher. Therefore potency for regeneration/ differentiation might begin when bio materials are displaced from the central position. In central position (at core), potential energy of self gravity is strongest. Metabolic or kinetic energy working against it fails to act in required differential function against the self gravity while locating itself as inner cell mass. Once it goes out of the inner cell mass, kinetic energy can set into motion leading to regeneration or differential of stem cell. This is similar to an example below. Kinetic energy of a frog for escape can be put to rest on pressing it at central position. On removal of pressure from central position, frog can go out to exhibit its full potency (Illustration 37). Same is the case for plasma cells83 which are large lymphocytes with a considerable nucleus-to-cytoplasm ratio. After the process of affinity maturation in germinal centers, plasma cells have an indeterminate lifespan, ranging from days to months. Recently they have been shown to reside for much longer periods in the bone marrow as long lived plasma cells (LLPC). Thus movement and lifespan of plasma cells depend on location and local characteristics within self gravitating environment.

39.  Metacenter and floating principle

Under floating condition, locating central position is dependent not only on the mass in question, but also on the density of the materials over which such mass floats. For a floating object to be stable, the center of gravity must be below the center of buoyancy. The metacenter is a line that intersects both the center of gravity and the center of mass.  The center of gravity may push the mass downward while the center of buoyancy may push the mass upward. When a fish, for example, is being rocked back and forth, center of gravity and center of buoyancy would come closer together thus decreasing the metacenter;  when center of buoyancy gets lower than center of gravity, the fish is going to flip (Illustration 38). 

40.  Neucleus and neucleolus- ‘core’ segment of the self gravitating interior

Neucleus and neucleolus under inverted colour of the photograph taken on using green fluorescent protein (GFP) tagged proteins80 shows that neucleus and neucleolus in vitro condition can be designated as the ‘core’ segment of the self gravitating interior of the living cell (Illustration 39).

41.  Change in concentric to eccentric nucleus under neutral buoyant condition

Deviation from centre or not having same centre is known as eccentricity. For instance, plasma cells are large lymphocytes with a considerable nucleus-to-cytoplasm ratio. They have basophilic cytoplasm and an eccentric nucleus84. Why such eccentric nucleus? Such eccentric nucleus is possible only when gravity-buoyancy equilibrium of a macromolecular solid core of nucleus deviates from the centre of the inertial frame of reference, as shown in the Illustration 40.

Gravitational attraction provides the restoring force that acts to return the eccentric core to its concentric position. Magnitude of the gravity force is proportional to the displacement D so long as the density of the outer fluid is constant in the integrated volume and the density distribution of the fluid in the remaining part of the vessel remains spherically symmetric as well as the average density of the core and the average density of the ?uid that surrounds the core52. Gravity is the force that helps to stabilize the central equilibrium position of the inner macromolecular spherical core. The Archimedes principle provides not valid but only an average approximation for the buoyancy force of comparatively solid nucleus submerged in cytoplasmic fluid when the size of the nucleus is much smaller than its distance away from the center of the surrounding matrix.

42.  Prototype of interior dynamics of self gravitating biomass

Let us draw a prototype84 of the internal gravitational dynamics of biomass. It has a core of radius R and mass mc bounded by structural membrane and filled with fluid with a density ρF.  The centre of the structure O is the origin of inertial frame of reference and displacement of the core D is from the origin. On orienting system of coordinates along the Z axis the displacement of the core could be measured.  The gravitational interaction between the core and the fluid in the interior structure can be determined by the gravitational attraction of the fluid contained inside the structure of radius R + D (Illustration 41). A paradigm of integration is presented below.

Due to the axial symmetry about the Z axis, only the Z components   will contribute to the total force FG. Considering (Illustration 50 Equation 16)

average density of the mass of the spherical core is (Illustration 50 Equation 17) , (Illustration 50 Equation 18), (Illustration 50 Equation 19), (Illustration 50 Equation 20)

The magnitude of the gravitational attraction is (Illustration 50 Equation 21)

The above result indicates that the magnitude of the gravity force of Mass2 is proportional to the displacement D, irrespective of comparative length of R so long as the density ρF of the fluid remain constant. When the R occupies the central position (D = 0) the gravitational force FG = 0 exactly as it was in the case of the pressure force FP. However, unlike the pressure force FP, for any non-zero value of D the resultant gravity force FG is always oriented toward the center of the structure O. It means that gravity is the force that helps to stabilize the central equilibrium position of the inner spherical core of Mass2. The Archimedes principle provides not valid but only an average approximation for the buoyancy force of nucleus submerged in surrounding fluid when the size of the nucleus is much smaller than its distance away from the center of the surrounding matrix.

Due to compression inside interior of the bounded structure, hydrostatic pressure increases with depth h from the surface according to the relationship: (Illustration 50 Equation 22)

where is density and  is the magnitude of the acceleration due to gravity at depth h. The magnitude of the gravity acceleration g is a known function of the radial distance r measured from the center of the structure: (Illustration 50 Equation 23)

where G is the gravitational constant. Combining these relationships (depth  and radius of the structure ), (Illustration 50 Equation 24)

where p is the pressure inside the structural interior and r is the radial distance, a function from the center of the structure. The expression for the radial pressure gradient is therefore

 (Illustration 50 Equation 25)

And since it is negative, it indicates that the pressure increases with depth for any radial density distribution ρ(r). At the core boundary the density of the ?uid is  and the pressure gradient is  (Illustration 50 Equation 26)

where  is the average density of the core. Inserting the expression for  gives the buoyancy force for in?nitessimally small D. For a near-concentric spherical core (D ≥ O  is the eccentricity), submerged in a spherically symmetric pressure gradient, the magnitude of the buoyancy force  (Illustration 50 Equation 27)

where R is the radius,  is the average density of the core, is the average density of the fluid that surrounds the core and   is gravitation constant.  The negative sign indicates that the buoyancy force FP pushes the structure away from the maximum pressure point at D = 0 for any D > 0. Therefore such limitations of the Archimedes principle needs to be accounted while calculating interactions of self gravity of living mass with planetary gravity considering the situation analogous to “planet within planet”.

General Property of Self Gravity

43. Self organization due to self gravity

We have already explained that self organization is the intrinsic property of self gravity. Biology cannot be exception, once we recognize the existence of self gravity in biology.  In a glass, of different liquids viz. honey, water, vegetable oil, alcohol can be organized one above other- thanks to earth’s gravity induced density gradient, as illustrated below (Illustration 42). 

Similar to aforesaid example of stratification of liquids in presence of extrinsic gravity, we can draw a hierarchy of biomaterials in a membrane-bound cell under the influence of self gravity. DNA sequences are transcribed into RNA and then translated into amino acid chains; the latter fold spontaneously into functional proteins. But genesis of spatial architecture, including how molecules find their proper location in cell space, the origins of supramolecular order, cell morphology are not yet satisfactorily answered1. The sequence of macromolecules> molecular self-assembly> pushing denser macromolecules outward> formation of twin centre of mass with decrease in mutual attraction can be expressed in coarse grain manner in the following, according to their timeline of formation.

It is common to see that nucleoid in prokaryote and nucleolis or nucleus in eukaryote- all are made of swarm of macromolecules. Depending upon the timeline of formation along other types of macromolecules, they would tend to lie in the central position due to priority of inward attraction of self gravity to drag higher molecular weight at the initial stage of cell growth. Such higher weight macromolecules subsequently become lighter than the equivalent volume of cytoplasmic fluid due to concentration of salts, matrix and therefore could float away to the outward periphery from the central position of self gravity due to side thrust generated by the co-moving denser fluids. At this late stage, denser macromolecules are pushes outward due to hydrostatic or turgor pressure. With the decrease in mutual attraction due to increase in distance, twin centre of mass forms, each exhibiting individual gravitating barrier (Illustration 43).

Energy producing organelles like mitochondria, chloroplast etc., though having a mixture of macromolecules having a combination of higher and lower molecular weight tend to remain little away from central position due to their mechanism for production of energy as a matter of local effect (Illustration 44). Molecular self-assembly or self organization is the direct as well as indirect consequence of the action of self gravity.

44.  Formation of twin centre of mass on decrease in mutual attraction

The centrosome is called the "microtubule organizing center".  Centrosomes in animals contain two orthogonally arranged centrioles.  The organelle is located near the nucleus in the cytoplasm due to potential energy of self gravity. It divides and migrates to opposite poles of the cell during mitosis. Pushing of denser macromolecules outward might be due to hydrostatic or turgor pressure develops during course of time (Illustration 45).

Gravitational force is a function of the radial distance from the core. With decrease in mutual attraction, twin centre of mass, as if two gravitating bodies, one outside the other’s gravity barrier could be formed. Location of pin-pointed centre of self gravity might be more defined in animal than in plant cell, where, in case later, effect of self gravity might be overshadowed by other local forces.

45. Self gravity dictates self organization of macromolecules in living cell  

Macromolecules are important for various biological functions. There are four basic kinds of biological macromolecules. These are carbohydrates, lipids, proteins and nucleic acids. These polymers are composed of different monomers. But one thing might get less attention that these macromolecules are having different molar mass or molecular weight in addition to variation in density. Under free floating condition, macromolecules having higher molar mass or higher density will occupy the core position of self gravitating body and macromolecules having intermediate or lesser molecular weight or lesser density will remain away from core. That is, ‘higher the density- higher would be the attractive force of self gravity’ or in reverse way ‘lesser the density - lesser would be the attraction of self gravity’. This is what is happening in the movement or position of macromolecules in the living cells in general, which testify that self gravity is operating in the living cell without any doubt. Alternative justifications in this regard are either absent or not elegant and well designed.

Let us assume that release of water molecules and presence of salts and other materials are ensured in the fluids from carbohydrates, proteins and other sources. Buoyant like forces automatically come into operation as a consequence of accumulation of fluid to a particular depth, thereby separating the rest biomass from the inertial external gravitational force. Under lifted or free floating condition, biological macromolecules having higher molar mass and density would be attracted first at the self gravity’s core, as higher the mass, higher would be the gravitational attraction. Compared to nucleic acid, molar mass of carbohydrate is less (say, galactose C6H12O6 is 180 g/mol. The molar mass, density and solubility of another carbohydrate C12H22O11 is 342.297 g/mol, 1.723 g/cm3 and 683.0 g/L respectively. On the other hand, molar mass of water (H2O) is 18 g/mol, sodium chloride (NaCl) - 58.443 g/mol and so on. Density of water is 1g/ml at 40C. So carbohydrates, water, salts possibly play effective primary role as ‘metabolically inert infrastructure’ or as foundation over which other macromolecules can ballet as per dictation of potential energy of self gravity and kinetic energy of the macromolecules. Under complex admixture of different macromolecules in various organelles, individual effects may not be pronounced. For the time being we are not bringing such admixture into our analysis. We left such analysis for the future.

For instance, in case of nucleic acid, molar mass of DNA fragments etc. is say, 1000–5,000,000 g/mol. Therefore under near free floating condition, nucleic acid which has higher molar mass or molecular weight as well as density, would tend to remain at the central core due to attraction of self gravity. It is to be noted that nucleic acids contain phosphorus, in addition to C, H, N & O. Unlike proteins, nucleic acids contained no sulfur. The DNA polymer is much larger and may extend up to 2 meters in length. The nucleus is only about 5μm in diameter. The chromosomal DNA is packed tightly and fit in that small volume. The molecular weight of double stranded DNA is approximately 660 x the number of base pairs. The genome of E. coli, for instance, contains 4,639,221 base pairs. The molecular weight of one E. coli genome, therefore, would be 660 x 4,639,221 = 2,840,000,000 g/mole. Molecular weights for the DNA from multicellular organisms are commonly 109 or greater. The DNA from the smallest human chromosome is over ten times larger than E. coli DNA. Therefore accumulation of nucleic acid under tightly packed condition at the central position possibly demonstrates presence of invisible force of self gravity without any contradiction.

Proteins,  on the other hand, which have intermediate molar mass or molecular weight as well as being comparatively less denser than nucleic acid, would remain in intermediate position under free floating condition as well as under self gravitating environment.  In case of fats and lipids, molar mass are also intermediate. But the density of fats and lipids is less than protein on equal volume basis. So fats and lipids are under duress of self gravity to occupy the peripheral position under ‘free movement’ (free fall) condition. Hence finding of lipids in cell membrane is not accidental, but a simple instance of comparatively delayed action of self gravity in attracting less dense materials compared to high dense materials at particular point of time (Illustration46). 

The molecular weight or molar mass and density of some amino acid and fatty acid are shown in Illustration 47 as Table 3 for ready reference.

46.  Globular protein form and self gravity

It is interesting that protein sphericity is not yet well defined though many studies are being conducted. Globular shapes, which are close to a sphere, often called spheroproteins, act as enzymes, hormones, transporters of other molecules, stocks of amino acids, and other roles, and they are the most interesting proteins in the design of drugs and understanding of life phenomenon. Let us extend the idea of self gravity towards such globular architecture of protein. 

Average protein density is a molecular-weight-dependent function85.  The spatial average density of proteins can be considered equal to 1.35 g/cm3 independent of the nature of the protein and particularly independent of its molecular weight. It is worthy to mention that proteins are composed of hydrophobic and hydrophilic amino acids.  As far as molar mass and density are concerned, there is no remarkable difference between hydrophobic and hydrophilic amino acids (Illustration 47 Table 3).  Hydrogen bonding between different atoms provides required force. However under free floating native aqueous environment, hydrophobic amino acids get buried in the core of a protein as ‘communal aggregation’ forming bonding between them, whereas hydrophilic amino acids could remain in the boundary of a protein for interaction with the aqueous solvent forming spherical structure. Thus being shielded by hydrophilic amino acids in the aqueous solvent, the hydrophobic amino acid seems to play a crucial role of sphericity with packing interactions on forming ‘communal aggregation’86. This general scenario sometimes gets changed. For example, the protein myoglobin87 contains 0.34 gram of iron in 100 grams of protein. The atomic weight of iron is 56; thus the minimum molecular weight of myoglobin is (56 × 100)/0.34 = about 16,500.  The minimum molecular weight of hemoglobin that contains four atoms of iron is 4 × 16,500 or 66,000. Thus if a protein contains only one molecule of one of the amino acids or one atom of iron, copper, or another element, the minimum molecular weight of the protein or a subunit differs and thereby their behavior in local self gravitating environment may slightly differ. 

47. Native conformation, denaturation and renaturation of protein and self gravity

After proteins get stabilized by hydrogen bonds, as revealed from above, the strength of dipole moment gets weaker with increase in distance from the central position. At that state, potential energy of self gravity gets increase with increase in mass. Therefore gravity gradients in the backbone of the polypeptide chains possibly tend to fold to a globular conformation at the ‘farthest point’ similar to ‘fountain effect’ with ‘central tendency’, thereby leading to folding in 3-dimensional secondary, tertiary or even quaternary structures of native conformation.

In this matter, it is worthwhile to note that formation of native conformation of protein cannot be based on simple classical chemical reactions but on a physical process, as can be seen from subsequent  ‘denaturation’ and ‘renaturation’ phenomena of proteins. The reverse process of native state in secondary and tertiary structure of protein is called as ‘denaturation’88. For protein ‘denaturation’, there is a need for application of some external physical stress or making protein thermally unstable possibly to the extent of overcoming gravity barrier of the self gravitating mass or putting in a compound such as a strong acid or base, a concentrated inorganic salt, an organic solvent like alcohol or chloroform. This is important to note that on short term basis, gravity is weaker than electrostatic force. Gravity works on mass at macromolecular level without any time frame. Protein aggregation is therefore a mass based aggregation (not charge based). Folding starts after formation of some critical mass that spread up to certain critical distance (say, 2.8-3.0 A0). Thus there is ample scope to doubt that phenomena could be propelled by the potential energy of self gravity, as it increases with increase in mass.

Again ‘denaturation’ of protein results in disruption in cell activity and possibly can proceed up to cell death. Why cell activity is to be disrupted, or cell death should occur with simple change in physical form, if chemistry is dominating?   It is interesting to note that under ‘renaturation’89, proteins can regain their native state when the denaturing influence is removed. So unless a universal binding force of self gravity is not brought into picture, native state of globular protein (‘naturation’), ‘denaturation’ and again reversing to its original form of  ‘renaturation’ will continue to remain elusive. So it is difficult to ignore invisible force of self gravity and hence it is gap area of investigation in life science.

48.  Some exceptions to general rule

Molar mass and density based thumb rule for action of the self gravity in organizing macromolecules may be violated by various local forces operating at particular period of formation, especially for proteins, lipids and others. For instance, hydrogen bonding, ionic interactions, Van Der Waals forces, and hydrophobic packing often might disturb the general pattern of attraction in protein macromolecules. Amyloids90 for instance, are insoluble fibrous protein aggregates sharing specific structural traits. They arise from at least 18 inappropriately folded versions of proteins and polypeptides present naturally in the body. These misfolded structures alter their proper configuration such that they erroneously interact with one another or other cell components forming insoluble fibrils. They have been associated with the pathology of more than 20 serious human diseases in that, abnormal accumulation of amyloid fibrils in organs may lead to amyloidosis, and may play a role in various neurodegenerative disorders. The site specific local environments of these proteins are required to be defined from the point of surrounding medium or metabolically inert infrastructure, apart from mass, volume and density of the cell or protein. The idea can be clear from the following facts.

49.  Spheroids fibrous protein and self gravity  

Though made up of almost same amino acids, the shape of fibrous proteins, often called scleroproteins, look like a long ?lament or rod, and usually serve as inert structural or storage protein. Keratin, collagen, elastin, and fibroin are all scleroproteins. Their role is limited to protection and support, forming connective tissue, tendons, bone matrices, and muscle fiber. Most of its polypeptide chain is parallel to a single axis and are often mechanically strong  and highly cross-linked. Under classic artefactual cell culture conditions in a flat, rigid petri dish or as per geometry of the contact surfaces, it remains in elongated position. It could possibly withstand the force of self gravity and remain in extended structure. But the behavior of cartilage cells, for instance, could be affected significantly when they are organized in 3-D using a micropatterning technique and on carefully positioning the cells within about 10 microns of each other i.e. nearly the diameter of a cell and about one-fifth the diameter of a human hair. Though process was observed to be slow or the size and shape of the cell clumps varied significantly, it is interesting that the cells clump together into "cell spheroids"91. From the above it is clear that spheroid shape could be formed due to potential energy of self gravity if there is free floating or free fall condition and self gravity is allowed to operate in unperturbed manner. As potential energy of self gravity and sphericity are two sides of the same coin, we can assume scleroproteins remain an exception only due to circumstances of local origin. So it could remain in extended structure, unlike compact form i.e it could possibly withstand the potential energy of self gravity. Manuel Théry92 while reviewing micropatterning as a tool to decipher cell morphogenesis and functions, pointed out that cell microenvironment, especially positioning of adjacent cells, location and orientation of extracellular matrix (ECM) fibres imposes specific ‘boundary conditions’ that influence cell architecture and mechanics. The size and stiffness of the microenvironment limits cell volume and cell spreading. However for geometrical control, only few studies have combined the soft, deformable substrates as medium. Hence environment that allows the self gravity to work unperturbed needs to be understood in better manner before drawing flat conclusion. 

50. Protein folding problem and topological property

The protein-folding problem was first posed about one half-century ago. Structural biology interprets molecular level biological mechanisms in terms of the structures of proteins and other biomolecules. Dill et al 93 made extensive reviews of protein folding problem. Understanding protein-folding "code" involves the question of a given string of amino acids lead to a particular balled-up ("native") structure of a protein. It is now understood that proteins fold rapidly because random thermal motions causing conformational changes leading energetically downhill toward the native structure, a principle that is captured in funnel-shaped energy landscapes.  The energy landscape is constructed by measuring the stabilities of folded fragments for a series of overlapping modular repeats. Each horizontal tier presents the partially folded fragments with the same number of repeats. Proteins  denature  at high  temperatures because  there  are many states of high  energy and  fewer states  of low energy,  that  is, the landscape is funneled. Thus ultimately folding speed of a protein is to be correlated with a topological property of its native structure. Why ultimately we are going to solve the problem through topological property?

51.  Proteins fold on funnel-shaped energy landscapes

Thus we can see that simple classical chemical reactions based on electrostatic force cannot solve the problem of protein folding. Albert Einstein thought that gravity is what happens when space itself is curved or warped around a mass, such as a star or a planet. Thus, a star or planet would cause kind of a dip in space so that any other object that came too near would tend to fall into the dip. Such curved geometry in spacetime governing the motion of inertial objects is being interpreted as gravity mainly generated by the mass of an object (Illustration 48 left). On the other hand, in funnel-shaped energy landscapes protein fold quickly due to random thermal motions causing conformational changes leading energetically downhill toward the native structure (right). An unfolded protein starts out in a state of high free energy that makes its conformation unstable. However, as the protein starts to fold, the free energy begins to drop and the number of possible conformations begins to decrease like the shrinking width of a funnel. The bottom of the funnel is reached when free energy is minimized. As the free energy drops, however, there may be kinetic traps along the way that can stop the folding process and hold the protein in partially folded conformations, known as molten globules and folding intermediates, for extended periods of time. Eventually these trapped conformational states are transformed into a stable conformation but the shape and form of that final conformation is influenced by the kinetic traps. It is a point of interest that such kinetic trap and potential energy of gravity has any relation. Because we know that aqueous solution of protein adopts three dimensional shapes that gives diverse pattern of protein folding having different size and shape of proteins in golf course, moat or other energy landscapes. Moreover varying solution conditions, such as hydration shells across the proteins, salt type, salt concentration, cosolutes, preservatives, surfactants affect this process apart from temperature and pH. Hence there is a need to study meticulously these external factors to ascertain is there is any universality or commonality in astrophysical and biological worlds. Here principle is important than miniature size.  This is high time to understand when and where do protein folds, whether with increasing potential energy of gravity at its central position, proteins are progressively directed towards increasingly low energies.

Continued to Part II  for more evidences including conclusion

Under the principle of abductive reasoning through successive approximation on sporadic set of observations, some more evidential roles of self gravity on identical astrophysical principles of larger mass have been conceptualized that are appended in part II of the present article. We are going to add our conclusions at the end of the Part II of the article. 


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