Cell-Size Control and Homeostasis in Bacteria

How cells control their size and maintain size homeostasis is a fundamental open question. Cell-size homeostasis has been discussed in the context of two major paradigms: “sizer,” in which the cell actively monitors its size and triggers the cell cycle once it reaches a critical size, and “timer,” in which the cell attempts to grow for a specific amount of time before division. These paradigms, in conjunction with the “growth law” [1] and the quantitative bacterial cell-cycle model [2], inspired numerous theoretical models [3–9] and experimental investigations, from growth [10, 11] to cell cycle and size control [12–15]. However, experimental evidence involved difficult-to-verify assumptions or population-averaged data, which allowed different interpretations [1–5, 16–20] or limited conclusions [4–9]. In particular, population-averaged data and correlations are inconclusive as the averaging process masks causal effects at the cellular level. In this work, we extended a microfluidic “mother machine” [21] and monitored hundreds of thousands of Gram-negative Escherichia coli and Gram-positive Bacillus subtilis cells under a wide range of steady-state growth conditions. Our combined experimental results and quantitative analysis demonstrate that cells add a constant volume each generation, irrespective of their newborn sizes, conclusively supporting the so-called constant Δ model. This model was introduced for E. coli [6, 7] and recently revisited [9], but experimental evidence was limited to correlations. This “adder” principle quantitatively explains experimental data at both the population and single-cell levels, including the origin and the hierarchy of variability in the size-control mechanisms and how cells maintain size homeostasis. [Display omitted] •Individual cells show systematic deviations from the population-level growth law•Cells sense neither space nor time but add constant mass, irrespective of birth size•The adder principle automatically ensures size homeostasis•All measured distributions collapse when rescaled by their respective means Taheri-Araghi et al. present extensive single-cell data from Gram-negative E. coli and Gram-positive B. subtilis showing that in both cases, cells add a constant volume, irrespective of birth size, and this automatically ensures size homeostasis.