Mechanical control of mitotic progression in single animal cells.

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.

authors

Cattin CJ,Düggelin M,Martinez-Martin D,Gerber C,Müller DJ,Stewart MP

doi

10.1073/pnas.1502029112

subject

Has Abstract

pub_date

2015-09-08 00:00:00

pages

11258-63

issue

36

eissn

0027-8424

issn

1091-6490

pii

1502029112

journal_volume

112

pub_type

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