期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：32
DOI：10.1073/pnas.2201328119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Most cells in the human body reside in a dormant state characterized by slow growth and minimal motility. During episodes such as wound healing, stem cell activation, and cancer growth, cells adapt to a more dynamic behavior characterized by proliferation and migration. However, little is known about the mechanical forces controlling the transition from static to motile following exit from dormancy. We demonstrate that keratinocyte monolayers install a mechanical system during dormancy that produces a coordinated burst of intercellular mechanical tension only minutes after dormancy exit. The activated forces are essential for large-scale displacements of otherwise motility-restricted cell sheets. Thus, cells sustain a mechanical system during dormancy that idles in anticipation of cell cycle entry and prompt activation of motion.
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.
