PT  - JOURNAL ARTICLE
AU  - Sara Kaliman
AU  - Maxime Hubert
AU  - Carina Wollnik
AU  - Lovro Nuić
AU  - Damir Vurnek
AU  - Simone Gehrer
AU  - Jakov Lovrić
AU  - Diana Dudziak
AU  - Florian Rehfeldt
AU  - Ana-Sunčana Smith
TI  - On the mechanical regulation of epithelial tissue homeostasis
AID  - 10.1101/2021.04.10.439119
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.10.439119
4099  - http://biorxiv.org/content/early/2021/04/11/2021.04.10.439119.short
4100  - http://biorxiv.org/content/early/2021/04/11/2021.04.10.439119.full
AB  - Despite recent efforts to understand homeostasis in epithelial tissues, there are many unknowns surrounding this steady state. It is considered to be regulated by mechanoresponse, but unlike for single cells, this remains heavily debated for tissues. Here, we show that changes in matrix stiffness induce a non-equilibrium transition from tubular to squamous Madin-Darby Canine Kidney II tissues. Nonetheless, despite different cell morphologies and densities, all homeostatic tissues display equivalent topologies, which, hence, must be actively targeted and regulated. On the contrary, the mechanoresponse induces dramatic changes in the large-scale organization of the colonies. On stiff gels, this yields an unreported cooperative state of motile cells displaying higher densities than in the arrested homeostatic state. This suggests a more complex relation between cell density and motility than previously anticipated. Our results unequivocally relate the mechanosensitive properties of individual cells to the evolving macroscopic structures, an effect that could be important for understanding the emergent pathologies of living tissues.Competing Interest StatementThe authors have declared no competing interest.