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 single Escherichia coli cells 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 birth-size, 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-than-average 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. ### Competing Interest Statement The authors have declared no competing interest.