Feedback linking cell envelope stiffness, curvature, and synthesis enables robust rod-shaped bacterial growth

Bacterial growth is remarkably robust to environmental fluctuations, yet the mechanisms of growth-rate homeostasis are poorly understood. Here, we combine theory and experiment to infer mechanisms by which Escherichia coli adapts its growth rate in response to changes in osmolarity, a fundamental physicochemical property of the environment. The central tenet of our theoretical model is that cell-envelope expansion is only sensitive to local information such as enzyme concentrations, cell-envelope curvature, and mechanical strain in the envelope. We constrained this model with quantitative measurements of the dynamics of E. coli elongation rate and cell width after hyperosmotic shock. Our analysis demonstrated that adaptive cell-envelope softening is a key process underlying growth-rate homeostasis. Furthermore, our model correctly predicted that softening does not occur above a critical hyperosmotic shock magnitude and precisely recapitulated the elongation-rate dynamics in response to shocks with magnitude larger than this threshold. Finally, we found that to coordinately achieve growth-rate and cell-width homeostasis, cells employ direct feedback between cell-envelope curvature and envelope expansion. In sum, our analysis points to new cellular mechanisms of bacterial growth-rate homeostasis and provides a practical theoretical framework for understanding this process. Significance StatementThe bacterial cell envelope is the critical structure that defines cell size and shape, and its expansion therefore defines cell growth. Although size, shape, and growth rate are important cellular variables that are robust to environmental fluctuations, the feedback mechanisms by which these variables influence cell-envelope expansion are unknown. Here, we explore how E. coli cells achieve growth-rate and cell-width homeostasis during fluctuations in osmolarity, a key environmental property. A biophysical model in which the cell envelope softens after an osmotic shock and envelope expansion depends directly on local curvature quantitatively recapitulated all experimental observations. Our study elucidates new mechanisms of bacterial cell morphogenesis and highlights the deep interplay between global cellular variables and the mechanisms of cell-envelope expansion.