Growth consequences of the inhomogeneous organization of the bacterial cytoplasm

In many bacteria, translating ribosomes are excluded from the nucleoid, while amino-acid and energy-supplying metabolic enzymes spread evenly throughout the cytoplasm. Here we show with time-lapse fluorescence microscopy that this inhomogeneous organisation of the cytoplasm can cause singleEscherichia colicells to experience an imbalance between biosynthesis and metabolism when they divide, resulting in cell size-dependent growth rate perturbations. After division, specific growth rate and ribosome concentration correlates negatively with birthsize, and positively with each other. These deviations are compensated during the cell-cycle, but smaller-than-average cells do so with qualitatively different dynamics than larger-thanaverage cells. A mathematical model of cell growth, division and regulation of biosynthetic and metabolic resource allocation reproduces our experimental findings, suggesting a simple mechanism through which long-term growth rate homeostasis is maintained while heterogeneity is continuously generated. This work shows that the life of single bacterial cells is intrinsically out-of-steady-state, dynamic and reliant on cytoplasmic organization.