期刊
CURRENT BIOLOGY
卷 25, 期 3, 页码 385-391出版社
CELL PRESS
DOI: 10.1016/j.cub.2014.12.009
关键词
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资金
- Paul G. Allen Foundation
- Pew Charitable Trusts
- National Science Foundation CAREER
- NIH [GM 64671]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1253843] Funding Source: National Science Foundation
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 A 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.
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