title: Cell-size control and homeostasis in bacteria.
abstract: 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.
authors.affiliation: Department of Physics, University of California San Diego, La Jolla, CA 92093.
authors.forename: Sattar
authors.initials: S
authors.lastname: Taheri-Araghi
authors.affiliation: Initiative for the Theoretical Sciences, The Graduate Center, City University of New York, 365 Fifth Ave., New York, NY 10016.
authors.forename: Serena
authors.initials: S
authors.lastname: Bradde
authors.affiliation: Department of Physics, University of California San Diego, La Jolla, CA 92093.
authors.forename: John T
authors.initials: JT
authors.lastname: Sauls
authors.affiliation: Department of Molecular & Cell Biology, University of California, Berkeley, CA 94720.
authors.forename: Norbert S
authors.initials: NS
authors.lastname: Hill
authors.affiliation: Department of Biology, Washington University, Saint Louis, MO 63130.
authors.forename: Petra A
authors.initials: PA
authors.lastname: Levin
authors.affiliation: Department of Systems Biology, Harvard Medical School, Longwood, MA 02115.
authors.forename: Johan
authors.initials: J
authors.lastname: Paulsson
authors.affiliation: Department of Physics, University of California San Diego, La Jolla, CA 92093.
authors.forename: Massimo
authors.initials: M
authors.lastname: Vergassola
authors.affiliation: Department of Physics, University of California San Diego, La Jolla, CA 92093.
authors.forename: Suckjoon
authors.initials: S
authors.lastname: Jun
mesh_terms: D004926:Escherichia coli / Q000166:cytology* / Q000254:growth & development*; D006706:Homeostasis / Q000502:physiology*; D008954:Models, Biological