Authors:
Sattar Taheri-Araghi, Serena Bradde, John T. Sauls, Norbert S. Hill, Petra Anne Levin, Johan Paulsson, Massimo Vergassola, & Suckjoon Jun
Summary:
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.
Source:
Current Biology; (12/24/14)