Natural selection for the optimal cytosolic density of a bacterial cell
The dry mass in the cytosol of a bacterial cell is composed of molecules of diverse sizes, spanning from tiny metabolites to large ribosomes. The dry mass density determines the diffusion of macro- and small-metabolites and also the catalytic efficiency of enzymes, and thereby determines the reaction fluxes. As a bacterial cell is optimized for fast growth, it must strike a balance between competing factors such as the density and distribution of the constituent molecules of the dry mass when allocating resources for their synthesis. Here we simulate a model cell to investigate how bacterial cells optimize their cytosolic density, accounting for the effects of molecular crowding on metabolic reactions. Our simplified model classifies molecular interactions into two groups: ribosomal reactions involving larger ribosomes and tRNAs, and metabolic reactions involving smaller globular enzymes and metabolites. We find that while higher density enhances encounter rates for metabolic reactions involving small molecules, lower density is preferred for ribosomal reactions involving larger molecules to facilitate better diffusion. Notably, our model predicts that large deviations from the optimal density lead to small reductions in growth rate. Moreover, our model's predictions of optimal density across different growth rates are consistent with the trends observed in experiments, such as the cytosolic density in E. coli cells cultured in both minimal and rich media. In sum, the cytosolic density of bacterial cells is governed by an optimality principle that aims at maximizing cellular efficiency.