A Preservation of Macromolecular Densities Defines Cell Width in Escherichia coli

All microbes demonstrate exquisite control over their shape and size. While a fundamental aspect of microbial life, our understanding of the biological and physical principles that underlie this control remains enigmatic despite its storied history of research in bacterial physiology. Seminal studies on cell size in rod-shaped, gram-negative organisms such as E. coli have culminated in a series of descriptive phenomenological models which capture important scaling relations, but remain separate from molecular details. Here, we present a novel model where the cell width is precisely adjusted such that macromolecular density within the periplasmic space is maintained across growth conditions. We test this hypothesis experimentally through a series of genetic and environmental perturbations which reveal this principle to be maintained. We quantitatively explore this hypothesis with a simple mathematical model that recapitulates classical scaling relationships, cementing the importance of cell width control in determining cell size. Finally, we consider explicit molecular players which may direct this control and its relationship and hypothesize how cell width- and length-control are interconnected.