Abstract
As a wound heals, or a body plan forms, or a tumour invades, observed cellular motions within the advancing cell swarm are thought to stem from yet to be observed physical stresses that act in some direct and causal mechanical fashion. Here we show that such a relationship between motion and stress is far from direct. Using monolayer stress microscopy, we probed migration velocities, cellular tractions and intercellular stresses in an epithelial cell sheet advancing towards an island on which cells cannot adhere. We found that cells located near the island exert tractions that pull systematically towards this island regardless of whether the cells approach the island, migrate tangentially along its edge, or paradoxically, recede from it. This unanticipated cell-patterning motif, which we call kenotaxis, represents the robust and systematic mechanical drive of the cellular collective to fill unfilled space.
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Acknowledgements
We thank L. Kobzik and D. Tschumperlin (Harvard University) and J. H. T. Bates (University of Vermont) for their critical comments. We thank D. Yu (MDACC) for creating stable MCF10A cell lines and M. H. Zaman for providing us with them. This research was supported by the Spanish Ministry for Science and Innovation (BFU2012-38146 and FPU fellowship XS), the Swiss National Science Foundation (PBEZP2-140,047), the National Research Foundation of Korea (2012R1A6A3A03040450), the European Research Council (Grant Agreement 242,993), Parker B. Francis (Fellowship RK), American Heart Association (13SDG14320004) and the National Institutes of Health (R01HL102373, R01HL107561).
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J.H.K. designed cellular migration experiments. X.S-P. and B.G performed staining experiments. J.H.K, X.S-P., D.T.T., M.S., E.H.Z, C.Y.P. and B.G carried out migration experiments and data analysis. D.T.T. contributed software. C.Y.P, J-A.P. and R.K. contributed to protocol designs. E.M. contributed to data analysis. J.P.B. and J.J.F. guided data interpretation and analysis. J.H.K., J.P.B., X.T. and J.J.F. wrote the manuscript. J.J.F. oversaw the project.
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Kim, J., Serra-Picamal, X., Tambe, D. et al. Propulsion and navigation within the advancing monolayer sheet. Nature Mater 12, 856–863 (2013). https://doi.org/10.1038/nmat3689
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DOI: https://doi.org/10.1038/nmat3689
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