Mechanical coupling of supracellular stress amplification and tissue fluidization during exit from quiescence

Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2201328119. doi: 10.1073/pnas.2201328119. Epub 2022 Aug 1.


Cellular quiescence is a state of reversible cell cycle arrest that is associated with tissue dormancy. Timely regulated entry into and exit from quiescence is important for processes such as tissue homeostasis, tissue repair, stem cell maintenance, developmental processes, and immunity. However, little is known about processes that control the mechanical adaption to cell behavior changes during the transition from quiescence to proliferation. Here, we show that quiescent human keratinocyte monolayers sustain an actinomyosin-based system that facilitates global cell sheet displacements upon serum-stimulated exit from quiescence. Mechanistically, exposure of quiescent cells to serum-borne mitogens leads to rapid amplification of preexisting contractile sites, leading to a burst in monolayer tension that subsequently drives large-scale displacements of otherwise motility-restricted monolayers. The stress level after quiescence exit correlates with the level of quiescence depth at the time of activation, and a critical stress magnitude must be reached to overcome the cell sheet displacement barrier. The study shows that static quiescent cell monolayers are mechanically poised for motility, and it identifies global stress amplification as a mechanism for overcoming motility restrictions in confined confluent cell monolayers.

Keywords: collective migration; epithelial monolayer; keratinocytes; mechanical forces; quiescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle* / physiology
  • Cell Division
  • Cell Proliferation
  • Homeostasis*
  • Humans
  • Keratinocytes* / cytology