Essential Role of Extrinsic Noise in Models of E. coli Division Control

Our understanding of cell division control in bacteria still relies largely on interpreting correlations between phenomenological variables, with limited connection to the underlying molecular mechanisms. Here, we analytically solve a stochastic threshold-accumulation model in which a size-dependent divisor protein triggers division upon reaching a noisy, autocorrelated threshold, quantifying within a unified framework the combined effects of intrinsic and extrinsic noise and key mechanistic parameters such as protein reset and threshold memory. We show that incorporating these elements yields behavior far richer than the commonly assumed adder, spanning a continuum of division strategies from timer to sizer while modulating size fluctuations in a nontrivial fashion. Comparison with single-cell E. coli data shows that extrinsic noise and additional mechanistic ingredients are required to account for the observed size fluctuations. The adder emerges when threshold correlations balance protein reset, generalizing the hypothesis that full reset is necessary to maintain adder control. Our results establish a unified analytical framework linking stochastic molecular processes to emergent division laws, to be used in more complex bacterial cell-cycle models.