Main principles of Ling's physical theory of the
living cell
Vladimir V. Matveev
Laboratory of Cell Physiology, Institute of Cytology, Russian Academy of
Sciences, Tikhoretsky Ave 4,
St. Petersburg 194064, Russia. E-mail:
vladimir.matveev @ gmail.com ;
personal web site: http://vladimirmatveev.ru
Full text [PDF] Full version
Purpose of the theory
The purpose of the theory is to establish the physical nature of the living
state. The theory explains the physical mechanisms underlying the key phenomenon
of life - the distribution of substances between the cell and its environment
and among cell compartments. Understanding of all other features (mechanisms
important for cell physiology and cell biology) depends crucially on our
understanding of this phenomenon.
Physical mechanisms that the theory uses
The theory describes electronic mechanisms that explain controlled selective
adsorption of ions and other substances at proteins and dynamic structuring of
water molecules by cell proteins. ATP, the principal cardinal adsorbate for
proteins, is the main regulator for both phenomena through induction (changes in
electron density of a protein molecule and then of other molecules associated
with it). The theory explains observed selective permeability, solute
accumulation and exclusion, volume changes in hypo- or hypertonic solutions and
cellular electrical potentials in an unifying manner.
Two-state model of cell function
According to the theory, the functioning of the cell or a part of the
cell is considered as a
reversible transition between two states, the resting state and the state of
activity. The resting state is a stable state (but sensitive to perturbations) with a favorable negative free
energy. Constant influx of energy and matter is not necessary to maintain this
state. The action of an external stimulus or internal signal is to destabilize
the resting state and the cell becomes active. The energy is released and is
used to perform biological functions. Metabolic processes start in the activated
cell, new ATP molecules are synthesized and the cell re-enters the resting
state. A cell in the resting state has a favorable negative free energy owing to
the adsorption energy of ATP bound by proteins. Activation of the cell starts
with the splitting of ATP. The two-state model can be applied to every structure
in the cell down to single protein molecules.
Which proteins determine the sorption properties of the cell?
In the resting state, fully extended proteins adsorb the key components (in the
physical sense) of the cell: ATP, water and potassium ions. According to the
contemporary literature, 30-40% of all cell proteins are natively unfolded
proteins. Perhaps these proteins (or some of them) belong to the set of fully
extended proteins considered by Ling's theory.
Physical nature of selective adsorption
The following functional groups of proteins have key significance for the
theory: the NH- and CO-groups of peptide bonds, and the carboxyl groups of
dicarboxylic amino acid residues. The selectivities of peptide groups differ
between the two states in respect of: (1) affinity for water molecules, and (2)
affinity for the same groups in other peptide bonds in the protein. The
selectivity of the carboxylic groups differs in respect of (1) affinity for
potassium ions, and (2) affinity for sodium ions or for fixed cationic groups of
the protein. The first state of the groups is inherent in the resting state of
the cell (or its parts). The second state indicates the active state of the
protein. The affinity depends on electron density in the considered functional
groups. Low density is characteristic of the resting state, high density of the
activated state. The main regulator of the electron density is ATP, which has
electron acceptor properties (Ca2+, signal factors, hormones, and chemical
modifications of proteins may also assist). In the resting state, ATP is
adsorbed
by protein and it displaces the electron density in the protein molecule to a
site where it is adsorbed. When ATP is split, the electron density in the
functional groups increases and their affinity becomes that of the second state.
Adsorption of water
The polypeptide backbone of any fully extended protein exhibits a
geometrically regular order of positive (NH) and negative (CO) charges of the
dipoles (similar to a one-dimensional crystal grid). This geometry is
complementary to a space between the water molecules surrounding the fully
extended protein. The complementarity creates conditions for multilayer
adsorption of water on the protein surface. As a result, much of the cellular
water (the most massive component of the cell, about 44 moles/l) is transformed
into an dynamically ordered structure (the entropy of the system is decreased).
Because of its interaction with the backbone dipoles, the dipole moment of the
adsorbed water is greater than that of free water. Water molecules with larger
dipole moments form stronger dipole-dipole interactions (hydrogen bonds are not
the only way in which water dipoles interact, but they are the major
contributors; if you consider all forces involved in the interaction, it is
better to talk about strengthening of the dipole-dipole interactions in
general). It is more difficult for molecules of a solute to break the stronger
interaction between molecules of adsorbed water, so this water is a poor solvent
compared to bulk water. Therefore, solutes are displaced from the volume of
adsorbed water into the free water space. Strongly adsorbed water is a barrier
to diffusion of large solutes and solutes with incompatible surface structures.
The water on the cell surface (rather than lipids) explains the property of cell
selective permeability. When you activate a resting cell or some its structure,
water is desorbed from the formerly fully extended proteins and the path for diffusion becomes
open. The selectivity of each functional group of the polypeptide backbone
changes from water to the other functional group of the backbone, and secondary
structures of the protein appear (alpha-helix, for example).
Adsorption of potassium ions
Potassium ions accumulate in the resting cell by selective adsorption by the
carboxyl groups of dicarboxylic amino acid residues. In the resting state
intracellular potassium ions (the most massive ions) are not free. Hence, the
observed stable osmotic equilibrium of a cell with an isotonic solution -
meaning equal water activity - is mainly a result of the specifically ordered
cell water structure. When the cell or part of the cell is activated by removal
of ATP from its protein adsorption sites, the carboxyl groups lose their
affinity for potassium ions and acquire greater selectivity for sodium ions or
to fixed cations of the protein. At the same time, the specifically ordered cell
water structure collapses. Potassium ions adsorbed by proteins in the
microscopically thin surface layer of a cell produce a resting electrical
potential. When the water in the surface layer is desorbed, the water barrier
collapses and external sodium ions enter the cell generating a sodium diffusion
potential. Sodium ions penetrate into the cell surface and displace potassium
ions from the adsorption sites. Potassium ions become free, forming a flow into
the environment and generating potassium diffusion potential. These two
diffusion potentials shape an action potential.
Structural unit of protoplasm
Protein molecules with bound ATP, water and potassium ions constitute a minimal
structure that preserves the basic physical properties of the whole living cell.
The vital activity of the cell is reduced to transitions (not a steady-state
regime) between the two states:
protein(ATP)m(H2O)n(K+)q
<---> protein + mADP + mPi + nH2O + qK+
The key consequences of the theory
The resting potential is the
result of the selective adsorption of potassium ions by proteins in the
microscopically thin surface layer of the cell.
The action potential is a result
of desorption of water from the microscopically thin cell surface protein layer
and the appearance of (1) a diffusion electrical potential of sodium ions
(influx), and then (2) potassium ions (efflux).
The cell is osmotically stable,
in equilibrium with an isotonic solution, owing to the bound state of water (not
because intracellular ions are free). In the resting state intracellular
potassium ions (the most massive ions) are not free.
The significance of Ling's theory for cell biology
Ling's theory is a revolutionary approach to solving the fundamental problems of
cell physiology and biology. It affords us a fresh look at old and modern
problems of biology. It is a new methodology of analysis of normal physiological
processes and cellular pathology. The distribution of Ling's theory through the
scientific community will give scientists an alternative view of the physical
mechanisms that are of principal importance for cell physiology, biology and
medicine.
See Ling's papers to follow the development of the theory
and its comparison with current views
Books
Ling, G.N.
A Physical Theory of the Living State: the Association-Induction Hypothesis.
Blaisdell: Waltham, Massachusetts, 1962.
Ling, G.N.
In Search of the Physical Basis of Life. Plenum Press: New York, 1984.
Ling GN: A Revolution in the Physiology of the Living Cell. Krieger Publ Co: Malabar FL: 1992.
Ling, G.N. Life at the Cell and Below-Cell Level. The Hidden History of a Fundamental Revolution in Biology. Pacific Press: New York, 2001.
Ling G.N. Physical Theory of the Living Cell. Unnoticed Revolution. Publishing House "Nauka": St.Petersburg, Russia, 2008. (Russian Edition).
Ling G.N.
What
is life in terms of the properties and activities of microscopic assemblies of
molecules, atoms, ions and electrons called nano-protoplasm. Cushing Malloy,
Inc., Ann Arbor, Michigan, 2013.
Selected articles
Ling, G. N. Oxidative phosphorylation and mitochondrial physiology: a critical review of chemiosmotic theory, and reinterpretation by the association-induction hypothesis. Physiol. Chem. Phys., 1981, 13, 29-96.
Ling, G. N.
A convergence of experimental and theoretical breakthroughs affirms the pm
theory of dynamically structured cell water on the theory’s 40th birthday.
In Water and the Cell (pp. 1-52). Springer Netherlands, 2006.
Ling, G. N.
History of the membrane (pump) theory of the living cell from Its beginning in
mid-19th century to Its disproof 45 years ago - though still taught worldwide
today as established truth. Physiol. Chem. Med. Med. NMR, 2007, 39, 1-67.
Ling, G. N.
Nano-protoplasm: the ultimate unit of life. Physiol. Chem. Phys. Med. NMR,
2007, 39, 111-234.
Ling, G. N.
A Historically significant study that at once disproves the membrane (pump)
theory and confirms that nano-protoplasm is the ultimate physical basis of life
- yet so simple and low-cost that it could easily be repeated in many high
school biology classrooms worldwide. Physiol. Chem. Phys. Med. NMR, 2008,
40, 89-113.
Ling's papers in the
journal "Physiological Chemistry and Physics
and Medical NMR".
Acknowledgments. I thank Gilbert Ling and Paul Agutter for valuable
comments on the manuscript.
May 17, 2012
Saint Petersburg, Russia
Full text [PDF]