Abstract
The physical dimensions of bacterial cells are finite, tightly regulated, and constrain phenotype based on cell surface area to volume ratios. Additionally, bacterial membranes have limited capacity to host proteins, constraining enzymatic potential per area. We combine these biophysical properties into an aggregate parameter termed specific membrane surface area (sMSA, nm2 gcdw−1) which is readily integrated into systems biology analyses including constraint-based stoichiometric models. sMSA-based analyses have remarkable agency to predict and interpret bacterial phenotypes including maximum growth rate, respiration efficiency, and potential for maintenance energy generation. The presented Escherichia coli research 1) quantitatively recreates the membrane proteome from central metabolism as a function of growth rate, 2) demonstrates that the maximum growth rate of both aerobic and anaerobic E. coli cultures abides by similar cell biology constraints including a Pareto tradeoff between simultaneous synthesis of biomass macromolecules and generation of maintenance energy, 3) quantifies the areal capacity of E. coli membranes to dissipate Gibbs energy during enthalpic and entropic dominated metabolisms, and 4) presents evidence that sMSA theory could permit isogenic populations to host multiple concurrent phenotypes with equivalent fitness metrics.The results support our sMSA theory, based on cell geometry and membrane enzyme capacity, as a substantial driver of
metabolism in both oxic and anoxic environments.