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Direct observation of mammalian cell growth and size regulation

Nature Methods volume 9, pages 910–912 (2012)Cite this article

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Abstract

We introduce a microfluidic system for simultaneously measuring single-cell mass and cell cycle progression over multiple generations. We use this system to obtain over 1,000 h of growth data from mouse lymphoblast and pro–B-cell lymphoid cell lines. Cell lineage analysis revealed a decrease in the growth rate variability at the G1-S phase transition, which suggests the presence of a growth rate threshold for maintaining size homeostasis.

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Figure 1: Measurement of single-cell growth and cell cycle progression.
Figure 2: Evidence for a growth rate threshold.

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Acknowledgements

We thank A. Miyawaki (RIKEN) for the mKO2-hCdt1 and mAG-hGem constructs, M. Stevens (MIT), M. Ginzberg and R. Kafri (Harvard Medical School) for valuable discussions and M. Chung (Harvard Medical School) for assistance with generating the FUCCI-labeled L1210 cells. S.R.M. acknowledges support from US National Cancer Institute contracts Physical Sciences Oncology Center U54CA143874 and R21 CA137695 as well as from the National Institutes of General Medical Sciences (NIGMS) EUREKA R01GM085457. M.W.K. acknowledges support from the NIGMS. S.S. acknowledges support from the Kwanjeong Educational Foundation, South Korea, through a graduate fellowship. Y.W. acknowledges support from a National Science Foundation Graduate Research Fellowship, and A.T. acknowledges support from The Marie Curie International Reintegration Grant PIRG-GA-2010-277062 and the Israeli Centers of Research Excellence (I-CORE) program (Center no. 41/11).

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Author notes

  1. Amit Tzur

    Present address: Present address: The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat-Gan, Israel.,

Authors and Affiliations

  1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA

    Sungmin Son, Yaochung Weng & Scott R Manalis

  2. Department of Mechanical Engineering, MIT, Cambridge, Massachusetts, USA

    Sungmin Son, Jisoo Kim & Scott R Manalis

  3. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA

    Amit Tzur, Paul Jorgensen & Marc W Kirschner

  4. Computational and Systems Biology Initiative, MIT, Cambridge, Massachusetts, USA

    Yaochung Weng & Scott R Manalis

  5. Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA

    Scott R Manalis

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  1. Sungmin Son
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Contributions

S.S. and Y.W. developed methods for multigeneration cell growth measurements. A.T. transformed the L1210 cell line with FUCCI. S.S., A.T., P.J., M.W.K. and S.R.M. designed the experiments and analyzed the data. S.S. developed an optical system for simultaneous fluorescence measurement and performed the experiments. J.K. assisted with the data acquisition and cell culture. S.S., A.T., Y.W., P.J., M.W.K. and S.R.M. wrote the manuscript.

Corresponding author

Correspondence to Scott R Manalis.

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Competing interests

S.R.M. is a cofounder of Affinity Biosensors, which develops techniques relevant to the research presented.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–14 (PDF 1632 kb)

Supplementary Video 1

An L1210 cell is repeatedly weighed by the SMR as described in Supplementary Figures 2, 11 and 12. (MOV 7818 kb)

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Son, S., Tzur, A., Weng, Y. et al. Direct observation of mammalian cell growth and size regulation. Nat Methods 9, 910–912 (2012). https://doi.org/10.1038/nmeth.2133

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