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.
journal_name
Proc Natl Acad Sci U S Aauthors
Cattin CJ,Düggelin M,Martinez-Martin D,Gerber C,Müller DJ,Stewart MPdoi
10.1073/pnas.1502029112subject
Has Abstractpub_date
2015-09-08 00:00:00pages
11258-63issue
36eissn
0027-8424issn
1091-6490pii
1502029112journal_volume
112pub_type
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