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  4. Mechanical control of mitotic progression in single animal cells

Mechanical control of mitotic progression in single animal cells

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Author(s)
Cattin, Cedric J.
•
Duggelin, Marcel
•
Martinez-Martin, David
•
Gerber, Christoph
•
Muller, Daniel J.
•
Stewart, Martin P
Date Issued
September 2015
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Cattin, Cedric J., Marcel Duggelin, David Martinez-Martin, Christoph Gerber, Daniel J. Muller, and Martin P. Stewart. “Mechanical Control of Mitotic Progression in Single Animal Cells.” Proc Natl Acad Sci USA 112, no. 36 (August 25, 2015): 11258–11263.
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Final published version
Abstract
Despite the importance of mitotic cell rounding in tissue development and cell proliferation, there remains a paucity of approaches to investigate the mechanical robustness of cell rounding. Here we introduce ion beam-sculpted microcantilevers that enable precise force-feedback–controlled confinement of single cells while characterizing their progression through mitosis. We identify three force regimes according to the cell response: small forces (∼5 nN) that accelerate mitotic progression, intermediate forces where cells resist confinement (50–100 nN), and yield forces (>100 nN) where a significant decline in cell height impinges on microtubule spindle function, thereby inhibiting mitotic progression. Yield forces are coincident with a nonlinear drop in cell height potentiated by persistent blebbing and loss of cortical F-actin homogeneity. Our results suggest that a buildup of actomyosin-dependent cortical tension and intracellular pressure precedes mechanical failure, or herniation, of the cell cortex at the yield force. Thus, we reveal how the mechanical properties of mitotic cells and their response to external forces are linked to mitotic progression under conditions of mechanical confinement.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
http://hdl.handle.net/1721.1/102101
DOI of Published Version
https://doi.org/10.1073/pnas.1502029112
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