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Propulsion and navigation within the advancing monolayer sheet

Nature Materials volume 12, pages 856–863 (2013)Cite this article

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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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Figure 1: Advancing monolayer of MDCK cells encounters and envelops a non-adherent island.
Figure 2: Orientations of tractions, velocities and principal stresses coincide, diverge and recover.
Figure 3: Cellular morphology, tight junction structure, and actin structure near the island.
Figure 4: Kenotactic tractions are evident in human mammary epithelial cells MCF10A vector, but are attenuated in MCF10A 14-3-3ζ, which disrupts adherens junctions.

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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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Authors and Affiliations

  1. School of Public Health, Harvard University, Boston, Massachusetts 02115, USA

    Jae Hun Kim, Dhananjay T. Tambe, Enhua H. Zhou, Chan Young Park, Monirosadat Sadati, Jin-Ah Park, Bomi Gweon, Emil Millet, James P. Butler & Jeffrey J. Fredberg

  2. Institute for Bioengineering of Catalonia, Barcelona 08028, Spain

    Xavier Serra-Picamal & Xavier Trepat

  3. Facultat de Medicina, Universitat de Barcelona, and Ciber Enfermedades Respiratorias, Barcelona 08036, Spain

    Xavier Serra-Picamal & Xavier Trepat

  4. Center for Vascular Biology Research, Harvard Medical School, Boston, Massachusetts 02215, USA

    Ramaswamy Krishnan

  5. Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 2115, USA

    James P. Butler

  6. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain

    Xavier Trepat

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  1. Jae Hun Kim
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Contributions

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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Correspondence to Jeffrey J. Fredberg.

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The authors declare no competing financial interests.

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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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