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Physical forces during collective cell migration

Nature Physics volume 5, pages 426–430 (2009)Cite this article

Abstract

Fundamental biological processes including morphogenesis, tissue repair and tumour metastasis require collective cell motions1,2,3, and to drive these motions cells exert traction forces on their surroundings4. Current understanding emphasizes that these traction forces arise mainly in ‘leader cells’ at the front edge of the advancing cell sheet5,6,7,8,9. Our data are contrary to that assumption and show for the first time by direct measurement that traction forces driving collective cell migration arise predominately many cell rows behind the leading front edge and extend across enormous distances. Traction fluctuations are anomalous, moreover, exhibiting broad non-Gaussian distributions characterized by exponential tails10,11,12. Taken together, these unexpected findings demonstrate that although the leader cell may have a pivotal role in local cell guidance, physical forces that it generates are but a small part of a global tug-of-war involving cells well back from the leading edge.

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Figure 1: Traction forces generated by a collectively migrating cell sheet.
Figure 2: Traction force distributions at different distances from the leading edge.
Figure 3: The state of stress of the whole expanding colony is set by a global tug-of-war.
Figure 4: Time fluctuations of tractions show cell–cell force transmission.

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Acknowledgements

We thank N. Gavara, R. Sunyer and C. Y. Park for experimental support and D. Tschumperlin and members of the Fredberg laboratory for insightful discussions.

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Authors and Affiliations

  1. Program in Molecular and Integrative Physiological Sciences, School of Public Health, Harvard University, Boston, Massachusetts 02115, USA

    Xavier Trepat, Michael R. Wasserman, Emil Millet, James P. Butler & Jeffrey J. Fredberg

  2. Unitat de Biofísica i Bioenginyeria, Universitat de Barcelona, Institute for Bioengineering of Catalonia, and Ciber Enfermedades Respiratorias, 08036 Barcelona, Spain

    Xavier Trepat

  3. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA

    Thomas E. Angelini & David A. Weitz

  4. Dept. Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA

    James P. Butler

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  1. Xavier Trepat
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  2. Michael R. Wasserman
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  3. Thomas E. Angelini
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  7. Jeffrey J. Fredberg
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Contributions

X.T., J.P.B. and J.J.F. designed research. X.T. and M.R.W. carried out experiments. J.P.B and X.T conducted theoretical analysis. T.E.A., D.A.W. and E.M. contributed to design protocols and data interpretation. X.T., J.P.B. and J.J.F. wrote the manuscript. J.P.B. and J.J.F. oversaw the project.

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Correspondence to Xavier Trepat or Jeffrey J. Fredberg.

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Trepat, X., Wasserman, M., Angelini, T. et al. Physical forces during collective cell migration. Nature Phys 5, 426–430 (2009). https://doi.org/10.1038/nphys1269

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