Mechanical control of mitotic progression in single animal cells

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 confinemen...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-09, Vol.112 (36), p.11258-11263
Main Authors: Cattin, Cedric J., Düggelin, Marcel, Martinez-Martin, David, Gerber, Christoph, Müllera, Daniel J., Stewart, Martin P.
Format: Article
Language:English
Subjects:
Actomyosin - metabolism
Animals
Biological Sciences
Cell division
Cell Shape
HeLa Cells
Histones - genetics
Histones - metabolism
Humans
Luminescent Proteins - genetics
Luminescent Proteins - metabolism
Mechanical properties
Microscopy, Atomic Force
Microscopy, Electron, Scanning
Microtubules - metabolism
Mitosis
Molecular Motor Proteins - genetics
Molecular Motor Proteins - metabolism
Myosin Heavy Chains - genetics
Myosin Heavy Chains - metabolism
Pressure
Reproducibility of Results
Single-Cell Analysis - instrumentation
Single-Cell Analysis - methods
Spindle Apparatus - metabolism
Tension
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1502029112