Optimal density of bacterial cells

A substantial fraction of the bacterial cytosol is occupied by catalysts and their substrates. While a higher volume density of catalysts and substrates might boost biochemical fluxes, the resulting molecular crowding can slow down diffusion, perturb the reactions' Gibbs free energies, and reduce the catalytic efficiency of proteins. Due to these tradeoffs, dry mass density likely possesses an optimum that facilitates maximal cellular growth and that is interdependent on the cytosolic molecule size distribution. Here, we analyze the balanced growth of a model cell, accounting systematically for crowding effects on reaction kinetics. Its optimal cytosolic volume occupancy depends on the nutrient-dependent resource allocation into large ribosomal vs. small metabolic macromolecules, reflecting a tradeoff between the saturation of metabolic enzymes, favoring larger occupancies with higher encounter rates, and the inhibition of the ribosomes, favoring lower occupancies with unhindered diffusion of tRNAs. Our predictions across growth rates are quantitatively consistent with the experimentally observed reduction in volume occupancy on rich media compared to minimal media in E. coli. Strong deviations from optimal cytosolic occupancy only lead to minute reductions in growth rate, which are nevertheless evolutionarily relevant due to large bacterial population sizes. In sum, cytosolic density variation in bacterial cells appears to be consistent with an optimality principle of cellular efficiency. Author summaryThe cellular cytosol harbours diverse molecules, whose crowding slows down diffusion and perturbs the chemical equilibrium of biochemical reactions. Reaction rates thus depend not only on the reactants themselves, but also on the background density of other molecules; as a consequence, maximal cell growth requires an optimal density. Here, we simulate a model cell with crowding-adjusted metabolic reaction kinetics. Its cytosol accommodates two types of reactions: metabolic reactions, involving small molecules, and protein production reactions that involve much larger molecules. These two cellular subsystems have distinct optimal densities, and a shift in their relative contribution to the cellular biomass explains the observed 10% difference in cytosolic density between E. coli bacteria growing in nutrient-rich and -poor environments.

Automated summary

A considerable amount of bacterial cytosol is filled with catalysts and their substrates. The optimal cytosolic volume occupancy depends on the allocation of resources and the balance between metabolic enzymes and ribosomes. The variation in cytosolic density in bacterial cells follows an optimality principle of cellular efficiency.