(264d) Membrane Surface Area Constrains Cell Maintenance Energy Generation

Cell growth requires significant fluxes for macromolecule synthesis and maintenance energy generation. A major theoretical concept in the study of metabolism, maintenance energy is cellular energy consumed for functions other than the direct production of biomass components. The magnitude of maintenance energy fluxes is inferred from physiological measurements and assumptions about the efficiency of metabolism. It is commonly applied as a fitting parameter in systems biology studies to ensure predicted fluxes align quantitatively with experimental fluxes. In this application, maintenance energy is usually assumed to increase monotonically with growth rate and nutrient flux. Yet is this a sound assumption, and furthermore, what are the ramifications if this assumption is incorrect?

Bacterial cell geometry constrains both the surface area and the volume available for metabolic enzymes. Additionally, the surface area to volume ratio changes with growth rate, altering the availability of surface area for essential processes including nutrient acquisition, generation of a proton motive force, and ATP synthesis. We applied a new in silico systems biology theory to quantify constraints imposed by cell geometry on the potential for maintenance energy generation. Experimental data from Escherichia coli cultures grown under glucose-limited, ammonium-limited, or iron-limited conditions were analyzed for maintenance energy fluxes. Applying a membrane surface area constraint suggests the commonly assumed linear relationship between maintenance energy and growth rate is inaccurate. Glucose-limited cultures had a nonlinear, positive relationship between growth rate and maintenance energy, iron limited cultures had a negative relationship between growth rate and maintenance energy, while ammonium-limited cultures had a hybrid relationship combining aspects of the glucose- and iron-limited trends. Ergo, duly accounting for cellular geometry could alter commonly held assumptions about bacterial metabolism.