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Biphasic growth dynamics control cell division in Caulobacter crescentus

Nature Microbiology volume 2, Article number: 17116 (2017) Cite this article

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Abstract

Cell size is specific to each species and impacts cell function. Various phenomenological models for cell size regulation have been proposed, but recent work in bacteria has suggested an ‘adder’ model, in which a cell increments its size by a constant amount between each division. However, the coupling between cell size, shape and constriction remains poorly understood. Here, we investigate size control and the cell cycle dependence of bacterial growth using multigenerational cell growth and shape data for single Caulobacter crescentus cells. Our analysis reveals a biphasic mode of growth: a relative timer phase before constriction where cell growth is correlated to its initial size, followed by a pure adder phase during constriction. Cell wall labelling measurements reinforce this biphasic model, in which a crossover from uniform lateral growth to localized septal growth is observed. We present a mathematical model that quantitatively explains this biphasic ‘mixer’ model for cell size control.

We recently introduced a technology that enables unprecedented amounts of precise quantitative information to be obtained about the shapes of single bacteria as they grow and divide under non-crowding and controllable environmental conditions1,2. Others have developed complementary methods3–6. These single-cell studies are generating great interest because they reveal unanticipated relationships between cell size and division control5. Recent work in bacteria has revealed a model of constant size increments between successive generations for a wide range of bacterial species3–5,7,8, as originally proposed in ref. 9 and recently termed an ‘adder’ model5,10. Competing models for size control include cell division close to a critical size (a ‘sizer’ model)11 or at a constant interdivision time (a ‘timer’ model), equivalent to a critical multiple of the birth size with a constant growth rate1. Analysis of single-cell data shows that cell size at division is positively correlated with the cell size at birth1,4,5,12,13, thus precluding a sizer model. In addition, a negative correlation between initial cell size and interdivision times, as reported here and in refs 1, 4, 5, 13 and 14, is inconsistent with the timer model. However, other studies have suggested mixed models of size control, with diverse combinations of sizer, timer and adder models10,15–17. The spatial resolution and statistically large size of our data now allow us to revisit these issues with greater precision.

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Figure 1: Cell size and division control in C. crescentus.
Figure 2: Crossover from relative timer to adder at the onset of cell wall constriction.
Figure 3: Crossover in cell wall growth dynamics at the onset of constriction.
Figure 4: The septal growth model predicts the onset of cell wall constriction and interdivision times.

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Acknowledgements

The authors thank C. Wright and S. Iyer-Biswas for measurements and shape analysis of C. crescentus single-cell data1,2. The authors thank S. Crosson and A. Fiebig for contributing reagents, materials and discussions. The authors acknowledge funding from the National Science Foundation Physics of Living Systems (NSF PHY-1305542), the National Science Foundation Materials Research Science and Engineering Center (MRSEC) at the University of Chicago (NSF DMR-1420709), the W. M. Keck Foundation and the Graduate Program in Biophysical Sciences at the University of Chicago (T32 EB009412/EB/NIBIB NIH HHS/United States). S.B. acknowledges support from the University College London for completion of part of this work.

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Authors and Affiliations

  1. James Franck Institute, The University of Chicago, Chicago, 60637, Illinois, USA

    Shiladitya Banerjee, Klevin Lo, Aaron R. Dinner & Norbert F. Scherer

  2. Department of Physics and Astronomy, University College London, London, WC1E 6BT, UK

    Shiladitya Banerjee

  3. Institute for the Physics of Living Systems, University College London, London, WC1E 6BT, UK

    Shiladitya Banerjee

  4. Institute for Biophysical Dynamics, The University of Chicago, Chicago, 60637, llinois, USA

    Klevin Lo, Matthew K. Daddysman, Alan Selewa, Aaron R. Dinner & Norbert F. Scherer

  5. Biophysical Sciences Graduate Program, The University of Chicago, Chicago, 60637, Illinois, USA

    Alan Selewa

  6. Department of Chemistry, The University of Chicago, Chicago, 60637, Illinois, USA

    Thomas Kuntz, Aaron R. Dinner & Norbert F. Scherer

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  1. Shiladitya Banerjee
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Contributions

S.B., K.L., A.R.D. and N.F.S. designed the research. S.B., K.L., A.S., M.K.D. and T.K. performed the research. S.B., A.R.D. and N.F.S. wrote the manuscript.

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Correspondence to Aaron R. Dinner or Norbert F. Scherer.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Notes 1–6, Supplementary Discussion, Supplementary References, Supplementary Figures 1–13. (PDF 21093 kb)

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Banerjee, S., Lo, K., Daddysman, M. et al. Biphasic growth dynamics control cell division in Caulobacter crescentus. Nat Microbiol 2, 17116 (2017). https://doi.org/10.1038/nmicrobiol.2017.116

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