000 02665 am a22003493u 4500
042 _adc
100 1 0 _aSonam, Surabhi
_eauthor
_92319
700 1 0 _aBalasubramaniam, Lakshmi
_eauthor
_92320
700 1 0 _aLin, Shao-Zhen
_eauthor
_92321
700 1 0 _aIvan, Ying Ming Yow
_eauthor
_92322
700 1 0 _aJaumà, Irina Pi
_eauthor
_92323
700 1 0 _aJebane, Cecile
_eauthor
_92324
700 1 0 _aKarnat, Marc
_eauthor
_92325
700 1 0 _aToyama, Yusuke
_eauthor
_92326
700 1 0 _aMarcq, Philippe
_eauthor
_92327
700 1 0 _aProst, Jacques
_eauthor
_92328
700 1 0 _aMège, René-Marc
_eauthor
_92329
700 1 0 _aRupprecht, Jean-François
_eauthor
_92330
700 1 0 _aLadoux, Benoît
_eauthor
_92331
245 0 0 _aMechanical stress driven by rigidity sensing governs epithelial stability
260 _c2023-01.
500 _a/pmc/articles/PMC7614076/
500 _a/pubmed/36686215
520 _aEpithelia act as a barrier against environmental stress and abrasion and in vivo they are continuously exposed to environments of various mechanical properties. The impact of this environment on epithelial integrity remains elusive. By culturing epithelial cells on 2D hydrogels, we observe a loss of epithelial monolayer integrity through spontaneous hole formation when grown on soft substrates. Substrate stiffness triggers an unanticipated mechanical switch of epithelial monolayers from tensile on soft to compressive on stiff substrates. Through active nematic modelling, we find that spontaneous half-integer defect formation underpinning large isotropic stress fluctuations initiate hole opening events. Our data show that monolayer rupture due to high tensile stress is promoted by the weakening of cell-cell junctions that could be induced by cell division events or local cellular stretching. Our results show that substrate stiffness provides feedback on monolayer mechanical state and that topological defects can trigger stochastic mechanical failure, with potential application towards a mechanistic understanding of compromised epithelial integrity during immune response and morphogenesis.
540 _a
540 _ahttps://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nNat Phys
856 4 1 _uhttp://dx.doi.org/10.1038/s41567-022-01826-2
_zConnect to this object online.
999 _c2243
_d2243