Abstract
The processes by which an organism develops its shape and heals wounds involve expansion of a monolayer sheet of cells. The mechanism underpinning this epithelial expansion remains obscure, despite the fact that its failure is known to contribute to several diseases, including carcinomas, which account for about 90% of all human cancers. Here, using the micropatterned epithelial monolayer as a model system, we report the discovery of a mechanical wave that propagates slowly to span the monolayer, traverses intercellular junctions in a cooperative manner and builds up differentials of mechanical stress. Essential features of this wave generation and propagation are captured by a minimal model based on sequential fronts of cytoskeletal reinforcement and fluidization. These findings establish a mechanism of long-range cell guidance, symmetry breaking and pattern formation during monolayer expansion.
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Acknowledgements
We thank M. Bintanel for technical assistance, S. Garcia and A. Carreras for help with polyacrylamide gels and micropatterning, the Nanotechnology Platform from Barcelona Science Park, J. J. Munoz for help with the numerical implementation of the model, and P. Roca-Cusachs, D.G. Miguez, D. Navajas, R. Farre and J. Alcaraz for discussions. This research was supported by the Spanish Ministry for Science and Innovation (BFU2009-07595 and FPU fellowship XS), the European Research Council (Grant Agreement 242993) and the National Institutes of Health (R01HL102373, R01HL107561).
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X.S-P. and X.T. designed experiments; X.S-P. performed all experiments. E.B. and X.S-P. performed gene expression experiments; X.S-P., R.V., V.C. and X.T. analysed data; D.T.T. contributed software; V.C. built the computer model and performed simulations; X.S-P., V.C., J.J.F. and X.T. wrote the manuscript; all authors discussed and interpreted results and commented on the manuscript; X.T. supervised the project.
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Serra-Picamal, X., Conte, V., Vincent, R. et al. Mechanical waves during tissue expansion. Nature Phys 8, 628–634 (2012). https://doi.org/10.1038/nphys2355
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DOI: https://doi.org/10.1038/nphys2355
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