Concerted control of Escherichia coli cell division

Significance The decisional process controlling cell division is a long-standing question in biology, but the answers were traditionally hindered by limited statistics on single cells. Contemporary experimental tools overcome this problem, but this progress must be combined with new theoretical tools to approach the data. This work introduces a quantitative method for estimating the variables controlling division rate and uses it to construct a minimal model from large-scale dynamic data on the size of dividing Escherichia coli cells. Cell size is found to be an important control variable of cell division, but not the sole one. Conversely, a description where division rate is determined jointly by cell size and time into the cell cycle reproduces well the available measurements. The coordination of cell growth and division is a long-standing problem in biology. Focusing on Escherichia coli in steady growth, we quantify cell division control using a stochastic model, by inferring the division rate as a function of the observable parameters from large empirical datasets of dividing cells. We find that (i) cells have mechanisms to control their size, (ii) size control is effected by changes in the doubling time, rather than in the single-cell elongation rate, (iii) the division rate increases steeply with cell size for small cells, and saturates for larger cells. Importantly, (iv) the current size is not the only variable controlling cell division, but the time spent in the cell cycle appears to play a role, and (v) common tests of cell size control may fail when such concerted control is in place. Our analysis illustrates the mechanisms of cell division control in E. coli. The phenomenological framework presented is sufficiently general to be widely applicable and opens the way for rigorous tests of molecular cell-cycle models.