The role of biomacromolecular crowding, ionic strength, and physicochemical gradients in the complexities of life's emergence

Abstract

We have developed a general scenario of prebiotic physicochemical evolution during the Earth's Hadean eon and reviewed the relevant literature. We suggest that prebiotic chemical evolution started in microspaces with membranous walls, where external temperature and osmotic gradients were coupled to free-energy gradients of potential chemical reactions. The key feature of this scenario is the onset of an emergent evolutionary transition within the microspaces that is described by the model of complex vectorial chemistry. This transition occurs at average macromolecular crowding of 20 to 30% of the cell volume, when the ranges of action of stabilizing colloidal forces (screened electrostatic forces, hydration, and excluded volume forces) become commensurate. Under these conditions, the macromolecules divide the interior of microspaces into dynamically crowded macromolecular regions and topologically complementary electrolyte pools. Small ions and ionic metabolites are transported vectorially between the electrolyte pools and through the (semiconducting) electrolyte pathways of the crowded macromolecular regions from their high electrochemical potential (where they are biochemically produced) to their lower electrochemical potential (where they are consumed). We suggest a sequence of tentative transitions between major evolutionary periods during the Hadean eon as follows: (i) the early water world, (ii) the appearance of land masses, (iii) the pre-RNA world, (iv) the onset of complex vectorial chemistry, and (v) the RNA world and evolution toward Darwinian thresholds. We stress the importance of high ionic strength of the Hadean ocean (short Debye's lengths) and screened electrostatic interactions that enabled the onset of the vectorial structure of the cytoplasm and the possibility of life's emergence.

FIG. 1.

The model of complex vectorial biochemistry in a cell. The cell wall is schematically represented as thick dark lines cross-linked with thin, wiggly vertical lines (peptidoglycan); below is the plasma membrane populated with various proteins and their complexes that control the interaction of the cell with the outside environment. Potential cytoskeleton proteins on the cytoplasmic side of the membrane are not shown. The cell wall, membrane, and cytoskeleton proteins comprise a cell's structural zone. At the bottom of the picture is DNA, to which various proteins are attached and which is surrounded by other proteins; the DNA is partially wound up and supercoiled on histone-like proteins. DNA and associated proteins form the replicative zone. In between is the transient structure of the proteome, with electrolyte pools and crowded regions of proteins and their complexes, which form the metabolic zone. Ionic currents are depicted by arrows. Biochemical metabolite flows arising from enzymatic reactions are designated by single double-arrowed lines between the crowded biomacromolecular regions and the electrolyte pools. Ionic flows between the pools, designated by two arrows in opposite directions, are driven by bulk electrochemical potentials between the pools. The biomacromolecular crowded regions act in effect as three-dimensional membranes between the electrolyte pools, which are permeable to cations and conditionally to some anions. (Biomacromolecular structures are adapted with permission of David S. Goodsell and the RCSB PDB.)

FIG. 2.

Comparable hydration layers and Debye's length. The green zone between 0.10 molar and 1.0 nm signifies the ranges of hydration and Debye's lengths that are commensurate with the surface-to-surface distances of protobiomacromolecules inside a crowded cell.

FIG. 3.

Distribution of protein abundance as a function of the predicted isoelectric point (pI). pI values were calculated for all proteins specified by the genome of Haloquadratum walsbyi (a halophile, living in an environment of high ionic strength and predicted to have a high intracellular ionic strength), Escherichia coli (a gram-negative bacterium, growing optimally at low to moderate salt concentrations, below 0.5 M NaCl) and Lactococcus lactis (a gram-positive bacterium, growing optimally at low to moderate salt concentrations). Both E. coli and L. lactis have an intracellular ionic strength that is low compared to that of H. walsbyi. The distribution of proteins as a function of pI is bimodal with a minimum around pH 7.5, i.e., corresponding to the intracellular pH of the cytoplasm. In the vast majority of microorganisms, anionic proteins are far more abundant than cationic ones. As shown for H. walsbyi, the bias for anionic proteins is most extreme in halophiles, that is, when the high external salt concentration is (osmotically) balanced by a high concentration of ionic osmolytes in the cytoplasm.