Threshold accumulation of a constitutive protein explains E. coli cell-division behavior in nutrient upshifts

Abstract

Despite a boost of recent progress in dynamic single-cell measurements and analyses in Escherichia coli, we still lack a mechanistic understanding of the determinants of the decision to divide. Specifically, the debate is open regarding the processes linking growth and chromosome replication to division and on the molecular origin of the observed "adder correlations," whereby cells divide, adding roughly a constant volume independent of their initial volume. In order to gain insight into these questions, we interrogate dynamic size-growth behavior of single cells across nutrient upshifts with a high-precision microfluidic device. We find that the division rate changes quickly after nutrients change, much before growth rate goes to a steady state, and in a way that adder correlations are robustly conserved. Comparison of these data to simple mathematical models falsifies proposed mechanisms, where replication-segregation or septum completions are the limiting step for cell division. Instead, we show that the accumulation of a putative constitutively expressed "P-sector divisor" protein explains the behavior during the shift.