Abstract

In nature, microorganisms exhibit different volumes spanning six orders of magnitude1. Despite their capability to create different sizes, a clonal population in a given environment maintains a uniform size across individual cells. Recent studies in eukaryotic and bacterial organisms showed that this homogeneity in cell size can be accomplished by growing a constant size between two cell cycle events (that is, the adder model2,3,4,5,6). Demonstration of the adder model led to the hypothesis that this phenomenon is a consequence of convergent evolution. Given that archaeal cells share characteristics with both bacteria and eukaryotes, we investigated whether and how archaeal cells exhibit control over cell size. To this end, we developed a soft-lithography method of growing the archaeal cells to enable quantitative time-lapse imaging and single-cell analysis, which would be useful for other microorganisms. Using this method, we demonstrated that Halobacteriumsalinarum, a hypersaline-adapted archaeal organism, grows exponentially at the single-cell level and maintains a narrow-size distribution by adding a constant length between cell division events. Interestingly, the archaeal cells exhibited greater variability in cell division placement and exponential growth rate across individual cells in a population relative to those observed in Escherichiacoli 6,7,8,9. Here, we present a theoretical framework that explains how these larger fluctuations in archaeal cell cycle events contribute to cell size variability and control.

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Acknowledgements

We thank T. Ursell for Morphometrics, D. B. Weibel for providing a fabrication facility, and K. A. Dulmage, M. Kapoor and W. Marshall for stimulating discussions. This work was supported by a Searle Scholars Award and NIH grant DP2AI117923-01 to E.C.G.; a HHMI Helen Hay Whitney Foundation Fellowship to Y.J.E.; the Harvard MRSEC program of the NSF DMR 14-20570 to P.H.; an A. P. Sloan Foundation grant and a Kavli Foundation grant to A.A.; and an NSF grant MCB-141-7750 and Duke Arts and Sciences Research Council Committee on Faculty Research grant to A.K.S., A.A., L.D.R. and E.C.G. also acknowledge support from the Volkswagen Foundation.

Author information

Affiliations

  1. Department of Molecular and Cellular Biology, Center for Systems Biology, Harvard University, Cambridge, MA, USA

    • Ye-Jin Eun
    • , Minjeong Kim
    •  & Ethan Garner
  2. School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    • Po-Yi Ho
    •  & Ariel Amir
  3. Leibniz Institute of Polymer Research and the Max Bergmann Center of Biomaterials, Dresden, Germany

    • Lars D. Renner
  4. Masconomet Regional High School, Boxford, MA, USA

    • Salvatore LaRussa
  5. INRA, UMR 1319 Micalis, Jouy-en-Josas, France

    • Lydia Robert
  6. AgroParisTech, UMR Micalis, Jouy-en-Josas, France

    • Lydia Robert
  7. Laboratoire Jean Perrin, UPMC-CNRS, UMR 8237, UPMC, Paris, France

    • Lydia Robert
  8. Biology Department, Center for Genomics and Computational Biology, Duke University, Durham, NC, USA

    • Amy Schmid

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Contributions

Y.-J.E., A.S., E.G. and A.A. conceived and designed the experiments. Y.-J.E., M.K., L.D.R. and S.L. performed the experiments. Y.-J.E., P.-Y.H., L.R. and A.A. analysed the data. Y.-J.E., P.-Y.H. and A.A. developed and evaluated the theoretical framework. Y.-J.E., P.-Y.H., L.D.R., L.R., A.S., E.G. and A.A. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Amy Schmid or Ethan Garner or Ariel Amir.

Supplementary information

  1. Supplementary Information

    Supplementary Tables 1–4, Supplementary Figures 1–9, Supplementary Notes.

  2. Life Sciences Reporting Summary

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    Halobacterium salinarum growth time-lapse.

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https://doi.org/10.1038/s41564-017-0082-6

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