General Quantitative Relations Linking Cell Growth and the Cell Cycle in Escherichia Coli

Abstract

Growth laws emerging from studies of cell populations provide essential constraints on global mechanisms coordinating cell growth. The foundation of bacterial cell cycle studies, based on extensive work done in Escherichia coli, relies on two interconnected dogmas proposed over 50-years ago: the SMK growth law that relates cell mass to growth rate1, and Donachie’s hypothesis of a growth-rate-independent initiation mass. These dogmas spurred many efforts to understand their molecular bases and physiological consequences5. While generally accepted in the fast-growth regime, i.e., for doubling times below one hour, extension of these dogmas to the slow-growth regime has never been consistently achieved. Through a quantitative physiological study of E. coli cell cycles over an extensive range of growth rates, here we report that neither dogma held in either the slow- or fast-growth regimes. In their stead, linear relations between the cell mass and the rate of chromosome replication/segregation were revealed that were valid over all growth rates. These relations led us to propose an integral-threshold model in which the cell cycle is controlled by a licensing process whose rate is related in a simple way to chromosomal dynamics. These results provide a quantitative basis for predictive understanding of cell growth-cell cycle relationships.