Abstract
The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells’ cytoskeleton, in the plasma membrane, or in cell–cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.
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Acknowledgements
We thank M. Bintanel, M. A. Rodríguez, J. Palou, E. Rebollo and N. Castro for technical assistance, the Nanotechnology platform at IBEC for microfabrication, P. Roca-Cusachs and members of the Trepat Lab for discussions, and B. Ladoux and J. De Rooij for plasmids and stable cell lines. This research was supported by the Spanish Ministry of Economy and Competitiveness (BFU2012-38146 to X.T., FIS-PI11/00089 to D.N.), the European Research Council (Grant Agreement 242993 to X.T., Grant Agreement 240487 to M.A.), and the National Institutes of Health (R01HL107561 to X.T.).
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L.C. and X.T. designed and implemented the experimental set-up. L.C., M.A. and X.T. designed the experiments, L.C. performed the experiments, and L.C. and R.V. analysed the experimental data. M.A. performed the theoretical analysis, D.Z. contributed technology, N.C. and D.N. decellularized the animal tissue, and L.C., M.A. and X.T. wrote the manuscript. All authors discussed and interpreted results, and commented on the manuscript.
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Casares, L., Vincent, R., Zalvidea, D. et al. Hydraulic fracture during epithelial stretching. Nature Mater 14, 343–351 (2015). https://doi.org/10.1038/nmat4206
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DOI: https://doi.org/10.1038/nmat4206
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