Regulation of cell elongation and division under fluctuating resource constraints

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Synopsis

Bacterial cells regularly face environmental variation in their natural habitats, and need to respond robustly and quickly to those fluctuations. In the rod-shaped bacterium Escherichia coli, steady-state cell shape has been shown to change in response to different nutrient conditions, through regulations of both cell elongation and division. However, it remains unclear how cells respond to continuous environmental changes and regulate cell shape. In this work, we develop a time-delay model that fully explains the dynamics of surface area and volume synthesis in a laboratory batch culture, which shows a universal set of dynamics of surface area to volume ratio (SA/V) for single-cell organisms. This model also predicts that SA/V is robust to division perturbations, but systematically changes with cell wall synthesis rates and translation rates, all of which have been experimentally verified. We then develop a mathematical model that quantiatively predicts the variation in cell shape across mutants based on shape-dependent changes to cell-cycle variables. Taken together, our work provides a quantitative framework for understanding cellular resource allocation, and has implications for how cells coordinate elongation and division under global resource constraints.