Mechanisms of cell size regulation in slow-growing Escherichia coli cells: discriminating models beyond the adder

Abstract Under ideal conditions, Escherichia coli cells divide after adding a fixed cell size, a strategy known as the adder . This concept applies to various microbes and is often explained as the division that occurs after a certain number of stages, associated with the accumulation of precursor proteins at a rate proportional to cell size. However, under poor media conditions, E. coli cells exhibit a different size regulation. They are smaller and follow a sizer-like division strategy where the added size is inversely proportional to the size at birth. We explore three potential causes for this deviation: degradation of the precursor protein and two models where the propensity for accumulation depends on the cell size: a nonlinear accumulation rate, and accumulation starting at a threshold size termed the commitment size . These models fit the mean trends but predict different distributions given the birth size. To quantify the precision of the models to explain the data, we used the Akaike information criterion and compared them to open datasets of slow-growing E. coli cells in different media. We found that none of the models alone can consistently explain the data. However, the degradation model better explains the division strategy when cells are larger, whereas size-related models (power-law and commitment size) account for smaller cells. Our methodology proposes a data-based method in which different mechanisms can be tested systematically.