Maintenance of cytoplasmic and membrane densities shapes cellular geometry in Escherichia coli.

Microbes precisely control their composition and geometry across diverse growth conditions, yet the mechanisms coordinating these processes remain unclear. Here, we integrate quantitative proteomics, microscopy, and biochemical measurements to reveal a biophysical principle linking these properties in Escherichia coli: cytoplasmic and membrane protein densities maintain a tightly conserved ratio across growth conditions, while the periplasmic density varies. Building on this observation, we develop a mathematical model demonstrating that maintaining this density ratio constrains the surface-to-volume ratio as a nonlinear function of proteome composition, specifically the ribosomal proteome fraction and partitioning between cellular compartments. The model holds under guanosine tetraphosphate perturbations that alter ribosome levels, further demonstrating that cellular geometry is not strictly determined by growth rate. These findings provide a biophysical framework for geometry control, underscoring density maintenance as a key physiological constraint that shapes cellular phenotypes.