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

  • Emma Lång
    Department of Microbiology, Oslo University Hospital, 0373 Oslo, Norway
  • Christian Pedersen
    Department of Mathematics, Mechanics Division, University of Oslo, 0851 Oslo, Norway
  • Anna Lång
    Department of Microbiology, Oslo University Hospital, 0373 Oslo, Norway
  • Pernille Blicher
    Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway
  • Arne Klungland
    Department of Microbiology, Oslo University Hospital, 0373 Oslo, Norway
  • Andreas Carlson
    Department of Mathematics, Mechanics Division, University of Oslo, 0851 Oslo, Norway
  • Stig Ove Bøe
    Department of Microbiology, Oslo University Hospital, 0373 Oslo, Norway

説明

<jats:p>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.</jats:p>

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