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Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding

Nature volume 469, pages 226–230 (2011)Cite this article

A Publisher Correction to this article was published on 26 June 2019

Abstract

During mitosis, adherent animal cells undergo a drastic shape change, from essentially flat to round1,2,3. Mitotic cell rounding is thought to facilitate organization within the mitotic cell and be necessary for the geometric requirements of division4,5,6,7. However, the forces that drive this shape change remain poorly understood in the presence of external impediments, such as a tissue environment2. Here we use cantilevers to track cell rounding force and volume. We show that cells have an outward rounding force, which increases as cells enter mitosis. We find that this mitotic rounding force depends both on the actomyosin cytoskeleton and the cells’ ability to regulate osmolarity. The rounding force itself is generated by an osmotic pressure. However, the actomyosin cortex is required to maintain this rounding force against external impediments. Instantaneous disruption of the actomyosin cortex leads to volume increase, and stimulation of actomyosin contraction leads to volume decrease. These results show that in cells, osmotic pressure is balanced by inwardly directed actomyosin cortex contraction. Thus, by locally modulating actomyosin-cortex-dependent surface tension and globally regulating osmotic pressure, cells can control their volume, shape and mechanical properties.

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Figure 1: Cells exert an increased rounding pressure in mitosis.
Figure 2: Mitotic cells require a functional actin cytoskeleton to generate rounding pressure.
Figure 3: The actomyosin cortex contracts against an intracellular osmotic pressure.
Figure 4: Animal cells control shape in mitosis by modulating intracellular pressure in conjunction with actomyosin activity.

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Acknowledgements

DFG, BMBF and SNF supported this project. JSPS supported Y.T. A.A.H. is funded by the Max Planck Society. We thank S. Bhakdi for toxins and advice on their use, T. J. Mitchison for extensive discussions on osmotic pressure and critical reading of the manuscript, M. Krieg for valuable insights into cell blebbing, and B. Baum, C. Brangwynne, S. Grill, A. Helenius, J. Howard, F. Jülicher, Z. Maliga and E. Paluch for discussions and critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Biosystems Science and Engineering, ETH Zürich, CH-4058 Basel, Switzerland,

    Martin P. Stewart, Jonne Helenius, Subramanian P. Ramanathan & Daniel J. Muller

  2. Biotechnology Center, University of Technology Dresden, D-01307 Dresden, Germany ,

    Martin P. Stewart

  3. Max-Planck-Institute of Molecular Cell Biology and Genetics, D-1307 Dresden, Germany ,

    Yusuke Toyoda & Anthony A. Hyman

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  1. Martin P. Stewart
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Contributions

M.P.S., D.J.M., Y.T. and A.A.H. designed and implemented the assay. M.P.S. performed the experiments except for the Young’s modulus measurements, which were made by J.H. S.P.R. contributed to Fig. 2 and Supplementary Fig. 6. Y.T. produced cell lines. J.H. designed the toxin experiments. M.P.S. analysed data and created the figures. M.P.S., J.H., D.J.M. and A.A.H. wrote the manuscript.

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Correspondence to Daniel J. Muller or Anthony A. Hyman.

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The authors declare no competing financial interests.

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This file contains Supplementary Figures 1-9 with legends, Supplementary Table 1, a Supplementary Discussion and additional references. (PDF 4704 kb)

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Stewart, M., Helenius, J., Toyoda, Y. et al. Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding. Nature 469, 226–230 (2011). https://doi.org/10.1038/nature09642

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