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

Abstract

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. Here we show that quiescent human keratinocyte monolayers contain an actinomyosin-based system that facilitates global viscoelastic flow upon serum-stimulated exit from quiescence. Mechanistically, serum exposure causes rapid amplification of pre-existing contractile sites leading to a burst in monolayer stress that subsequently drives monolayer fluidization. The stress magnitude after quiescence exit correlates with quiescence depth, and a critical stress level must be reached to overcome the cell sheet displacement barrier. The study shows that static quiescent cell monolayers are mechanically poised for motility and identifies global stress amplification as a mechanism for tissue fluidization.