TY  - BOOK
AU  - Sonam,Surabhi
AU  - Balasubramaniam,Lakshmi
AU  - Lin,Shao-Zhen
AU  - Ivan,Ying Ming Yow
AU  - Jaumà,Irina Pi
AU  - Jebane,Cecile
AU  - Karnat,Marc
AU  - Toyama,Yusuke
AU  - Marcq,Philippe
AU  - Prost,Jacques
AU  - Mège,René-Marc
AU  - Rupprecht,Jean-François
AU  - Ladoux,Benoît
TI  - Mechanical stress driven by rigidity sensing governs epithelial stability
PY  - 2023///-01
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7614076; /pubmed/36686215
N2  - Epithelia 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
UR  - http://dx.doi.org/10.1038/s41567-022-01826-2
ER  -