Mechanical control of mitotic progression in single animal cells

Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11258-63. doi: 10.1073/pnas.1502029112. Epub 2015 Aug 25.


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.

Keywords: cell confinement; cell cortex; mitotic arrest; mitotic cell rounding; mitotic progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism
  • Animals
  • Cell Shape
  • HeLa Cells
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • 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
  • Reproducibility of Results
  • Single-Cell Analysis / instrumentation*
  • Single-Cell Analysis / methods*
  • Spindle Apparatus / metabolism*


  • Histones
  • Luminescent Proteins
  • MYH9 protein, human
  • Molecular Motor Proteins
  • Actomyosin
  • Myosin Heavy Chains