Living cells, the basic units of all life, are primarily water, proteins, and K; they exist in an environment containing primarily water and Na+. Components of the living cell are in constant exchange with those in the external medium. A person travelling to England is soon filled with English water, English K+--, etc., yet the traveller does not change his or her character nor identity. Thus the living being and its component cells owe their identity and uniqueness not to the molecular components themselves but to the forces and mechanisms that determine their unique composition. The theories for these forces and mechanisms are focussed on the clear segregation between living cells and their environments of the two chemically almost indistinguishable ions, K+ and Na+. According to the membrane-pump theory, cell K+ and water are free; high cell K+ and low cell Na+ result from continual pumping by energy-consuming pumps in the cell membrane. According to the association induction hypothesis, both K+ and water in cells are adsorbed, K+ singly on anionic side chains of intracellular proteins; water in multilayers by matrix proteins with extended polypeptide chains. Low solubility of large and complex molecules in this polarized water accounts for the low level of Na+, Ca++, sugar, etc., in cells. To test these theories I have chosen 5 different projects which represent either new discoveries or old ones that have long defied interpretation: (1) The reuptake of K+ and extrusion of Na+ by resealed red cell ghosts depends critically on the volume of the lysing solution. (2) The binding of K+ (and Na+) by proteins in vitro sharply increases with pH rise and the K+ or Na+ taken up exchanges with nonlabelled ions in the surrounding medium much more slowly than ions in the presence of native protein. (3) The free Ca++ concentrations to elicit contraction reported in the literature are 2 orders of magnitude apart from each other. (4) The resting potential of muscle cells can change from being cation (K+) sensitive to anion (C1-) sensitive under a variety of conditions and no good explanation has been so far established. (5) Exhaustive stimulation of frog muscles raises the osmotic activity of the cells to a level so high that it has not been possible to explain the data on the basis of conventional wisdom. These 5 projects, seemingly unconnected to one another, are major clues toward solution of the complex, but highly coherent """"""""crossword"""""""" puzzle of the life phenomenon.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM011422-20
Application #
3268261
Study Section
Physiology Study Section (PHY)
Project Start
1977-06-01
Project End
1986-07-31
Budget Start
1985-07-01
Budget End
1986-07-31
Support Year
20
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Pennsylvania Hospital (Philadelphia)
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Ling, G N (1988) Solute exclusion by polymer and protein-dominated water: correlation with results of nuclear magnetic resonance (NMR) and calorimetric studies and their significance for the understanding of the physical state of water in living cells. Scanning Microsc 2:871-84
Ling, G N (1988) A physical theory of the living state: application to water and solute distribution. Scanning Microsc 2:899-913
Ling, G N; Ochsenfeld, M M (1987) Studies on the physical state of water in living cells and model systems. VI. Concentration-dependent sustained volume changes of dialysis sacs containing aqueous solution of native and denatured protein, gelatin, and oxygen-containing polymers immersed i Physiol Chem Phys Med NMR 19:177-92
Ling, G N (1987) Studies on the physical state of water in living cells and model systems. VII. Exclusion of sugars and sugar alcohols from the water in sulfonate ion exchange resins: the ""size rule"". Physiol Chem Phys Med NMR 19:193-8
Ling, G N (1987) On the large error introduced in the estimate of the density of membrane pores from permeability measurements when diffusion in ""unstirred layer"" within the cells is disregarded. Physiol Chem Phys Med NMR 19:199-207
Ling, G N (1987) Cell volumes and water contents of frog muscles in solutions of permeant sugars and sugar alcohols. Physiol Chem Phys Med NMR 19:159-75
Ling, G N; Reid, C; Murphy, R C (1986) Are the proteins in malignant cancer cells of diverse origin similar or different? Physiol Chem Phys Med NMR 18:147-58
Ling, G N; Ochsenfeld, M M (1986) Membrane lipid layers vs. polarized water dominated by fixed ions: a comparative study of the effects of three macrocyclic ionophores on the K+ permeability of frog skeletal muscle, frog ovarian eggs, and human erythrocytes. Physiol Chem Phys Med NMR 18:109-24
Ling, G N (1986) Cooperative interaction among surface beta- and gamma-carboxyl groups mediating the permeation of ions into frog muscle cells. Physiol Chem Phys Med NMR 18:125-9
Ling, G N (1986) The role of inductive effect in the determination of protein structure. Physiol Chem Phys Med NMR 18:3-16