Abstract
Cells comprising a tissue migrate as part of a collective. How collective processes are coordinated over large multi-cellular assemblies has remained unclear, however, because mechanical stresses exerted at cell–cell junctions have not been accessible experimentally. We report here maps of these stresses within and between cells comprising a monolayer. Within the cell sheet there arise unanticipated fluctuations of mechanical stress that are severe, emerge spontaneously, and ripple across the monolayer. Within that stress landscape, local cellular migrations follow local orientations of maximal principal stress. Migrations of both endothelial and epithelial monolayers conform to this behaviour, as do breast cancer cell lines before but not after the epithelial–mesenchymal transition. Collective migration in these diverse systems is seen to be governed by a simple but unifying physiological principle: neighbouring cells join forces to transmit appreciable normal stress across the cell–cell junction, but migrate along orientations of minimal intercellular shear stress.
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Acknowledgements
For their critical comments, we thank R. Hubmayr (Mayo Clinic), R. Phillips (CalTech), D. Navajas (University of Barcelona), L. B. Freund (Brown University), D. Tschumperlin (Harvard University), C. Forbes Dewey, Jr (MIT) and V. B. Shenoy (Brown University). We acknowledge the support of the European Research Council (Starting Grant FP7/ERC-242993), the Spanish Ministry of Science and Innovation (BFU2009-07595) and the National Institutes of Health (R01HL102373, R01HL107561, R01CA132633). We thank D. Yu (MDACC) for the kind gift of MCF-10A cell lines.
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D.T.T. developed algorithms and performed stress measurements. C.C.H. analysed data pertaining to force chains and glassy dynamics. D.T.T. and T.E.A. performed measurements of cell motions. K.R. and C.Y.P. assisted in protocol design and optimization. C.Y.P. performed staining of actin cytoskeleton. X.S-P. performed additional stress measurements on MDCK cells. M.H.Z. provided cancer cell lines and assisted with related data interpretation. D.T.T. and E.H.Z. made early conceptual contributions. J.P.B., D.A.W., J.J.F. and X.T. guided data interpretation and analysis. D.T.T., C.C.H., J.P.B., X.T. and J.J.F. wrote the manuscript.
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Tambe, D., Corey Hardin, C., Angelini, T. et al. Collective cell guidance by cooperative intercellular forces. Nature Mater 10, 469–475 (2011). https://doi.org/10.1038/nmat3025
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DOI: https://doi.org/10.1038/nmat3025
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