Information forgotten or overlooked: fundamental flaws in the conventional view of the living cell.Hazlewood CF
AbstractOld ideas often persist long after sound evidence dictates otherwise. I attempt to report one such case in the life sciences, by pointing out what are perceived to be fundamental flaws or questions in conventional wisdom. It is my experience that much evidence not in support of the well accepted membrane pump view of the living cell has been overlooked, forgotten or even ignored. In presenting this idea, the evolution of our knowledge from the establishment of cellular and protoplasmic theory to the emergence of solution theory is presented.
The universal hypothesis based on physical chemical principles is presented, followed by the advent of the membrane-situated energy-requiring pump. The experimental demonstration of an inadequate energy supply for the first pump is discussed, followed by a review of new evidence that calls to question the use of dilute solution theory in describing adequately cellular function. Finally, roles for cellular water are suggested to explain the cellular exclusion of sodium and to serve as a barometer for the healthy state. Within the context of a metaphor, I attempt to qualitatively embrace the physical findings. It is concluded that the mobility of water molecules may be considered to change with the progression of normal tissue to a state of disease. These changes in the mobility of water molecules are “fingerprinted” by changes in the molecular motion of the solids.
2. Biochim Biophys Acta. 2008 Dec;1778(12):2655-70. Epub 2008 Sep 12.
Structural and functional properties of hydration and confined water in membrane interfaces.Disalvo EA, Lairion F, Martini F, Tymczyszyn E, Frías M, Almaleck H, Gordillo GJ.
AbstractThe scope of the present review focuses on the interfacial properties of cell membranes that may establish a link between the membrane and the cytosolic components. We present evidences that the current view of the membrane as a barrier of permeability that contains an aqueous solution of macromolecules may be replaced by one in which the membrane plays a structural and functional role.
Although this idea has been previously suggested, the present is the first systematic work that puts into relevance the relation water-membrane in terms of thermodynamic and structural properties of the interphases that cannot be ignored in the understanding of cell function. To pursue this aim, we introduce a new definition of interphase, in which the water is organized in different levels on the surface with different binding energies. Altogether determines the surface free energy necessary for the structural response to changes in the surrounding media. The physical chemical properties of this region are interpreted in terms of hydration water and confined water, which explain the interaction with proteins and could affect the modulation of enzyme activity. Information provided by several methodologies indicates that the organization of the hydration states is not restricted to the membrane plane albeit to a region extending into the cytoplasm, in which polar head groups play a relevant role. In addition, dynamic properties studied by cyclic voltammetry allow one to deduce the energetics of the conformational changes of the lipid head group in relation to the head-head interactions due to the presence of carbonyls and phosphates at the interphase. These groups are, apparently, surrounded by more than one layer of water molecules: a tightly bound shell, that mostly contributes to the dipole potential, and a second one that may be displaced by proteins and osmotic stress.
Hydration water around carbonyl and phosphate groups may change by the presence of polyhydroxylated compounds or by changing the chemical groups esterified to the phosphates, mainly choline, ethanolamine or glycerol. Thus, surface membrane properties, such as the dipole potential and the surface pressure, are modulated by the water at the interphase region by changing the structure of the membrane components.
An understanding of the properties of the structural water located at the hydration sites and the functional water confined around the polar head groups modulated by the hydrocarbon chains is helpful to interpret and analyze the consequences of water loss at the membranes of dehydrated cells. In this regard, a correlation between the effects of water activity on cell growth and the lipid composition is discussed in terms of the recovery of the cell volume and their viability. Critical analyses of the properties of water at the interface of lipid membranes merging from these results and others from the literature suggest that the interface links the membrane with the aqueous soluble proteins in a functional unit in which the cell may be considered as a complex structure stabilized by water rather than a water solution of macromolecules surrounded by a semi permeable barrier.
3. Physiol Chem Phys Med NMR. 2007;39(2):111-234.
Nano-protoplasm: the ultimate unit of life.Ling G
AbstractAmong the most promising scientific achievements of the 19th century was the recognition that the laws governing the dead world also govern the world of the living and that life has a physical basis called protoplasm. Regrettably, the definition of protoplasm provided then was (inescapably) incorrect, offering a (legitimate) reason for rejecting the concept of protoplasm by an overwhelming majority of later investigators, teachers and other opinion-makers. Without a recognized physical basis, Life itself also faded into the limbo of the unexplainable.
However, eventually the needed relevant parts of physics and chemistry to give a more cogent definition of protoplasm became available. That then made possible the construction in the early 1960′s of a unifying theory of the living cell, named the association-induction (AI) hypothesis. Historically speaking, the AI Hypothesis is the heir to the general concept of protoplasm as the physical basis of life-incorrect as the initial definition of protoplasm was notwithstanding. In the AI Hypothesis (AIH) the true or ultimate physical basis of life is not what the advocates of the protoplasm once considered as the physical basis of life. What they saw and construed as the physical basis of life is a particular kind of macroscopic protoplasm. In the AI Hypothesis, the basic unit (or physical basis) of life is microscopic protoplasm or nano-protoplasm, of which all macroscopic protoplasm is made.
The AI Hypothesis also had no difficulty offering a new definition to what life is in terms of fundamental physical-chemical laws. Nano-protoplasm is defined by what it is and what it does. In greater detail, it is defined (i) by its chemical composition given in Equation 1 on p. 124; (ii) by the mutual spatial and energetic relationships among the components as illustrated diagrammatically in Figure 5 on p. 125; and (iii) by the ability of these components to exist as coherent assemblies in either one of two alternative states, the resting and active living (or dead) state as according to Equation 5 on p. 142. The review then describes the AIH-based electronic and molecular mechanisms for the coherent assemblage of the components, for the maintenance of the living states and for the auto-cooperative transitions between the resting and active (or dead) living state.
Having completed the theoretical section, the review goes on to describe the experimental testing of the theory carried out in the past forty-some years (and even in time before that by authors who knew nothing of the theory.) These experimental studies fall into two broad categories. In the first category, are the experiments performed on ultra-simple models of nano-protoplasm made up from pure chemicals as prescribed in Equation 1 on p. 124.
The results show that they indeed behave qualitatively like that illustrated in Figure 5 and quantitatively follow the dictates of Equation 5. In the second category of experimental testing, parallel studies were carried out on nano-protoplasm as part of living cells–in carrying out each one of the four classical functions of cell physiology: (1) solute and water distribution; (2) solute and water permeability; (3) cellular resting and action potentials; (4) cellular swelling and shrinkage. The results show that the nano-protoplasm in situ too qualitatively behave like that shown in Figure 5 and quantitatively follow the dictates of Equation 5. The review ends on a discussion section, examining how cogent do the experimental data accumulated thus far support to the AI version of the concept of nano-protoplasm as the most basic unit of life.