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Biphasic growth dynamics control cell division in Caulobacter crescentus

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.

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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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References

  1. Iyer-Biswas, S. et al. Scaling laws governing stochastic growth and division of single bacterial cells. Proc. Natl Acad. Sci. USA 111, 15912–15917 (2014).

    Article  CAS  PubMed Central  Google Scholar 

  2. Wright, C. S. et al. Intergenerational continuity of cell shape dynamics in Caulobacter crescentus. Sci. Rep. 5, 9155 (2015).

    Article  CAS  PubMed Central  Google Scholar 

  3. Wang, P. et al. Robust growth of Escherichia coli. Curr. Biol. 20, 1099–1103 (2010).

    Article  CAS  PubMed Central  Google Scholar 

  4. Campos, M. et al. A constant size extension drives bacterial cell size homeostasis. Cell 159, 1433–1446 (2014).

    Article  CAS  PubMed Central  Google Scholar 

  5. Taheri-Araghi, S. et al. Cell-size control and homeostasis in bacteria. Curr. Biol. 25, 385–391 (2015).

    Article  CAS  PubMed Central  Google Scholar 

  6. Sauls, J. T., Li, D. & Jun, S. Adder and a coarse-grained approach to cell size homeostasis in bacteria. Curr. Opin. Cell Biol. 38, 38–44 (2016).

    Article  CAS  PubMed Central  Google Scholar 

  7. Amir, A. Cell size regulation in bacteria. Phys. Rev. Lett. 112, 208102 (2014).

    Article  Google Scholar 

  8. Deforet, M., van Ditmarsch, D. & Xavier, J. B. Cell-size homeostasis and the incremental rule in a bacterial pathogen. Biophys. J. 109, 521–528 (2015).

    Article  CAS  PubMed Central  Google Scholar 

  9. Voorn, W., Koppes, L. & Grover, N. Mathematics of cell division in Escherichia coli. Curr. Top. Mol. Genet. 1, 187–194 (1993).

    Google Scholar 

  10. Jun, S. & Taheri-Araghi, S. Cell-size maintenance: universal strategy revealed. Trends Microbiol. 23, 4–6 (2015).

    Article  CAS  PubMed Central  Google Scholar 

  11. Schaechter, M., Williamson, J. P., Hood, J. Jr & Koch, A. L. Growth, cell and nuclear divisions in some bacteria. J. Gen. Microbiol. 29, 421–434 (1962).

    Article  CAS  PubMed Central  Google Scholar 

  12. Koppes, L., Meyer, M., Oonk, H., De Jong, M. & Nanninga, N. Correlation between size and age at different events in the cell division cycle of Escherichia coli. J. Bacteriol. 143, 1241–1252 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Osella, M., Nugent, E. & Lagomarsino, M. C. Concerted control of Escherichia coli cell division. Proc. Natl Acad. Sci. USA 111, 3431–3435 (2014).

    Article  CAS  Google Scholar 

  14. Tanouchi, Y. et al. A noisy linear map underlies oscillations in cell size and gene expression in bacteria. Nature 523, 357–360 (2015).

    Article  CAS  PubMed Central  Google Scholar 

  15. Donachie, W., Begg, K. & Vicente, M. Cell length, cell growth and cell division. Nature 264, 328–333 (1976).

    Article  CAS  Google Scholar 

  16. Kubitschek, H. Bilinear cell growth of Escherichia coli. J. Bacteriol. 148, 730–733 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Harris, L. K. & Theriot, J. A. Relative rates of surface and volume synthesis set bacterial cell size. Cell 165, 1479–1492 (2016).

    Article  CAS  PubMed Central  Google Scholar 

  18. Wang, J. D. & Levin, P. A. Metabolism, cell growth and the bacterial cell cycle. Nat. Rev. Microbiol. 7, 822–827 (2009).

    Article  CAS  PubMed Central  Google Scholar 

  19. Mitchison, J. M. The Biology of the Cell Cycle (CUP Archive, 1971).

    Google Scholar 

  20. Marshall, W. F. et al. What determines cell size? BMC Biol. 10, 101 (2012).

    Article  PubMed Central  Google Scholar 

  21. Banerjee, S., Scherer, N. F. & Dinner, A. R. Shape dynamics of growing cell walls. Soft Matter 12, 3442–3450 (2016).

    Article  CAS  PubMed Central  Google Scholar 

  22. Lin, Y., Li, Y., Crosson, S., Dinner, A. R. & Scherer, N. F. Phase resetting reveals network dynamics underlying a bacterial cell cycle. PLoS Comput. Biol. 8, e1002778 (2012).

    Article  CAS  PubMed Central  Google Scholar 

  23. Ursell, T. S. et al. Rod-like bacterial shape is maintained by feedback between cell curvature and cytoskeletal localization. Proc. Natl Acad. Sci. USA 111, E1025–E1034 (2014).

    Article  CAS  PubMed Central  Google Scholar 

  24. Aaron, M. et al. The tubulin homologue FtsZ contributes to cell elongation by guiding cell wall precursor synthesis in Caulobacter crescentus. Mol. Microbiol. 64, 938–952 (2007).

    Article  CAS  PubMed Central  Google Scholar 

  25. Kuru, E. et al. In situ probing of newly synthesized peptidoglycan in live bacteria with fluorescent d-amino acids. Angew. Chem. Int. Ed. 51, 12519–12523 (2012).

    Article  CAS  Google Scholar 

  26. Reshes, G., Vanounou, S., Fishov, I. & Feingold, M. Cell shape dynamics in Escherichia coli. Biophys. J. 94, 251–264 (2008).

    Article  CAS  PubMed Central  Google Scholar 

  27. Sibarita, J.-B. in Microscopy Techniques (ed. Rietdorf, J. ) 201–243 (Springer, 2005).

    Book  Google Scholar 

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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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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.

Corresponding authors

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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