The early development of many organisms involves the folding of cell monolayers, but this behaviour is difficult to reproduce in vitro; therefore, both mechanistic causes and effects of local curvature remain unclear. Here we study epithelial cell monolayers on corrugated hydrogels engineered into wavy patterns, examining how concave and convex curvatures affect cellular and nuclear shape. We find that substrate curvature affects monolayer thickness, which is larger in valleys than crests. We show that this feature generically arises in a vertex model, leading to the hypothesis that cells may sense curvature by modifying the thickness of the tissue. We find that local curvature also affects nuclear morphology and positioning, which we explain by extending the vertex model to take into account membrane–nucleus interactions, encoding thickness modulation in changes to nuclear deformation and position. We propose that curvature governs the spatial distribution of yes-associated proteins via nuclear shape and density changes. We show that curvature also induces significant variations in lamins, chromatin condensation and cell proliferation rate in folded epithelial tissues. Together, this work identifies active cell mechanics and nuclear mechanoadaptation as the key players of the mechanistic regulation of epithelia to substrate curvature.
S.G. acknowledges funding from FEDER Prostem Research Project no. 1510614 (Wallonia DG06), F.R.S.-FNRS Epiforce Research Project no. T.0092.21 and Interreg MAT(T)ISSE project, which is financially supported by Interreg France-Wallonie-Vlaanderen (Fonds Européen de Développement Régional, FEDER-ERDF). This project was supported by the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme grant agreement 851288 (to E.H.), and by the Austrian Science Fund (FWF) (P 31639; to E.H.). L.R.M. acknowledges funding from the Agence National de la Recherche (ANR), as part of the ‘Investments d’Avenir’ Programme (I-SITE ULNE/ANR-16-IDEX-0004 ULNE). This work benefited from ANR-10-EQPX-04-01 and FEDER 12001407 grants to F.L. W.D.V. is supported by the Research Foundation Flanders (FWO 1516619N, FWO GOO5819N, FWO I003420N, FWO IRI I000321N) and is member of the Research Excellence Consortium µNEURO at the University of Antwerp. M.L. is financially supported by FRIA (F.R.S.-FNRS). M.S. is a Senior Research Associate of the Fund for Scientific Research (F.R.S.-FNRS) and acknowledges EOS grant no. 30650939 (PRECISION). Sketches in Figs. 1a and 5e and Extended Data Fig. 9 were drawn by C. Levicek.
Luciano M, Xue S, De Vos WH, et al. Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation. Nature Physics. 2021;17(12):1382–1390. doi:10.1038/s41567-021-01374-1
Luciano, M., Xue, S., De Vos, W. H., Redondo-Morata, L., Surin, M., Lafont, F., … Gabriele, S. (2021). Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-021-01374-1
Luciano, Marine, Shi-lei Xue, Winnok H. De Vos, Lorena Redondo-Morata, Mathieu Surin, Frank Lafont, Edouard B Hannezo, and Sylvain Gabriele. “Cell Monolayers Sense Curvature by Exploiting Active Mechanics and Nuclear Mechanoadaptation.” Nature Physics. Springer Nature, 2021. https://doi.org/10.1038/s41567-021-01374-1.
M. Luciano et al., “Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation,” Nature Physics, vol. 17, no. 12. Springer Nature, pp. 1382–1390, 2021.
Luciano M, Xue S, De Vos WH, Redondo-Morata L, Surin M, Lafont F, Hannezo EB, Gabriele S. 2021. Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation. Nature Physics. 17(12), 1382–1390.
Luciano, Marine, et al. “Cell Monolayers Sense Curvature by Exploiting Active Mechanics and Nuclear Mechanoadaptation.” Nature Physics, vol. 17, no. 12, Springer Nature, 2021, pp. 1382–1390, doi:10.1038/s41567-021-01374-1.
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