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Biophysical Processes in Healthy and Cancer Cells

Nature of Life

Life exists in a great variety of forms. The simplest living systems are very likely viruses. Mammals may be regarded as the most advanced living systems. The great family of living creatures differs in many aspects especially in the complexity and hierarchical organization. Neural activity connected with the highest form of life is one of the most striking features. Research of biochemistry and molecular biology has disclosed a great amount of fundamental data about biological systems. Nevertheless, science has to formulate the general law governing the life — the coherent electrodynamic state.

Coherent Electrodynamic State — Necessary Condition for Life

Coherent electrodynamic state excited and maintained by energy supply far from thermodynamics equilibrium is a nature of life. Fröhlich (1968a, b; 1969; 1973; 1980) formulated a hypothesis that the coherent electrodynamic state is formed by coherent electric polar vibrations. In eukaryotic cells microtubules form the generating structure (Pokorný et al. 1997; Pokorný and Wu 1998). Pelling et al. (2004; 2005) measured coherent vibrations of yeast cells by atomic force microscope in the acoustic frequency range. Kasas et al. (2015) investigated vibration of different types of cells with a conclusion, that vibrations are a signature of life. Jelínek et al. (2009) found that frequencies of vibrations and electric oscillations coincide. Using dielectrophoretic effect Pohl (1981) experimentally proved that the highest power level of oscillations is in the M phase of the cell cycle. Direct measurement of the electromagnetic field in the frequency range 8—9 MHz of the synchronized yeast cell S. cerevisiae in the M phase disclosed the increased power in the period of mitotic spindle formation, metaphase, and anaphase A and B (Pokorný et al. 2001). Electromagnetic field may mediate interactions between living cells. Interaction forces between red blood cells acting up to a distance of about 1 μm were measured by Rowlands (1988). Sahu et al. (2013a, 2014) measured resonance frequencies of separated microtubules in the bandwidths 100 kHz—20 GHz, far infrared, and UV region.

Filamentous Structures — Material Medium

Typical representative of molecules with a filamentous structure are proteins. Amino acids are joined together by a rigid planar peptide bond. The structure of a protein is not stable and unique. A protein can assume a large amount of different conformational substates which can be described by the energy landscape (Frauenfelder, 2005). Transition between different conformational substates can result in different dynamics and function of the protein. Deformability of macromolecules provides sensitivity to the surrounding medium. Conformational substates can be used as a memory for storing data. Preliminary measurement of microtubules disclosed capability of storing data into microtubules. Sahu et al. (13b) measured about 500 bits with 2 pA resolution and current between 1 nA and 1 pA. But the real memory should be much higher. A tubulin monomer has about N = 7500 atoms and about M = 460 peptide bonds. Assuming that each atom may occupy two different positions the number of states is 2N. If the configurations differ in energy then each of them forms a bit of memory. The total capacity corresponds to about 1030 TB. If each peptide bond link may have about 10 positions due to rotation changes of dihedral angles then the capacity of the memory may be about the same. This represents an elementary rough assessment of possible capacity of a cell memory in a microtubule component.

Electric Polarity of Molecules

Electric polarity depends on distribution of charge in the macromolecular structure. The peptide bond is an electric dipole whose inner electric field is oriented from nitrogen to oxygen. Two types of charges were analyzes in amino acids. One type is formed by ionized side chains, the other type by partial atomic charges - each atom has some fraction of a positive or a negative charge, which depends on electronegativity of the atom. The positively charged amino acids side chains are in Lys, Arg, His, and negatively charged in Asp and Glu. The polarity with partial atomic charges is formed in the side chains of Asn, Gln, Ser, Thr, Tyr. The most important protein structure in eukaryotic cells is formed by microtubules built from heterodimers consisting from two monomers called α and β tubulin. Each heterodimer represents an electric dipole originating from 18 calcium ions bound within each β monomer (Satarić et al. 1993; Tuszyński et al. 1995). An equal number of negative charges (electrons) is localized in the neighboring α monomer. After polymerization the main component of the dipole vector is oriented along the axis of microtubule from its — to + end. Hydrolysis of GTP to GDP in the β tubulin changes its conformation and position of the β tubulin is tilted with respect to α tubulin and the main component of the dipole moment reverses orientation. Frequencies of electric resonant oscillations in microtubules were measured in the classical frequency bands 100 kHz—20 GHz, far infrared region around 500—700 cm−1, and UV band around 300 nm by Sahu et al. (13a; 14).

Energy Supply

Energy supply to living systems excites and maintains the coherent electrodynamic state far from the thermodynamic equilibrium. Energy may be supplied from water, sunlight, radiation in the far infrared, infrared, visible, and UV bands, by conduction of heat, from energy rich molecules, etc. Life exists at the bottom of the sea around active volcanic sources. In mammalian cells conversion of energy of glucose and fatty acids into energy bonds of ATP and GTP is a dominant process. Glucose is cleaved into two pyruvates with a net gain of two ATP molecules by glycolysis (fermentation). Pyruvates and fatty acids are processed by oxidative metabolism in mitochondria.

Energy is supplied to microtubules by several mechanisms and processes (Pokorný et al. 2013). Energy supplied by hydrolysis of GTP to GDP in the β tubulin after polymerization is a basic process. Energy supply by treadmilling in the M phase is more than one order of magnitude greater than that in the interphase by growth and shrinking of microtubules. Energy is supplied by motor proteins moving along microtubules. Non utilized energy liberated from mitochondria may be also used. Photons released from chemical reactions in the UV and visible part of the wavelength spectrum are a source of energy too. Excess thermal energy which was not utilized for building of coherent domains may also excite vibrations.

Energy supply to microtubules is a crucial point of the whole cell’s metabolic turnover. Lamprecht (1980) disclosed by calorimetric investigations that under optimal conditions a yeast cell of S. cerevisiae obtains power of 10−13 W. Mammalian cell may obtain higher power but on average not exceeding 10−12 W. Microtubule excitation in a mammalian cell is assessed to be of the order of magnitude of 10−13 W.

Water Ordering

Water constitutes 70 % of the total mass of a cell and its function is essential for life. The liquid phase of water was generally assumed to be preserved in living cells. But water has extraordinary properties which were not known and are undoubtedly necessary for the living state. The physical analysis of water is based on quantum electrodynamics (Del Giudice et al. 1988; Voeikov 2007; Arani et al. 1995; Del Giudice et al. 2009a, b). Coherent interaction of water molecules with quantized radiation of electromagnetic field results in a macroscopic permanent polarization. Random thermal fluctuations are transformed into coherent dynamic state of interacting electrons in water molecules and formation of coherent domains (CD) which are able to interact mutually. Experimental research performs measurement of the water layers at charged surfaces (Voeikov 2007; Zheng and Pollack 2003; Zheng et al. 2006; Pollack et al. 2006; Chai et al. 2009). Electric field at the charged surfaces provides arrangement of CDs into ordered layer. The layer is called exclusion zone — the solvent particles are excluded from the ordered layer. Strong static electric field of about 600—700 kV/m organizes water and forms a floating water bridge about 1—3 cm long between two glass beakers (Fuchs et al. 2007, 2008; Giuliani et al. 2009).

CD’s with linear dimension about 100 nm are formed at the physiological temperature. Energy with high entropy from the environment is transformed into energy with low entropy. The energy of a molecule in the CD is lower than in the bulk water. CD is formed when superfluous energy is transferred to the outside. CD of water is able to transform the whole amount of collected energy without thermal losses in chemical reactions.

CD is formed when thermal energy is transferred into coherent oscillation of electrons in single molecules between two different configurations, i.e. between a fundamental state (with energy 12.60 eV to release an electron) and a coherent state excited by energy 12.06 eV (and energy 0.54 eV to free an electron). The coherent state displays tendency to yield electrons and the fundamental state (incoherent state) to produce H2O ions. Ordered water has a gel-like structure, high viscosity, lowered thermal motion, pH and spectroscopic properties different from bulk water, and separation of charge.

Infrared radiation from ordered water is reduced. Measurement was performed by an infrared-camera with the spectral window of 3.8—4.6 μm and at 200 frames/s sampling rate. Temperature noise equivalent 0.015 K was limited by camera noise (Zheng et al. 2006). Averaging of 100—200 frames reduced temperature noise equivalent to 0.001 K which corresponds to noise energy k*T = 1.38*10−26 Ws. In living cells extremely low power could be distinguished from noise.

Water ordering affects cell function by separation of charge, low damping of electric polar vibrations and generated electromagnetic field, low noise (the temperature noise equivalent is less than 1 K), and by release of energy.

Conclusion

The coherent electrodynamic state far from thermodynamic equilibrium is a necessary condition of life and represents a unique property of each living entity. The state is excited and maintained by continuous energy supply. The living systems are different and the basic attributes, i.e. the sources of energy, filamentous and oscillating structures, electric polarity, and water ordering correspond to the life entity.

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