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Emerging modes of collective cell migration induced by geometrical constraints

  1. Benoît Ladouxa,d,2
  1. aMechanobiology Institute, National University of Singapore, Singapore 117411;
  2. bNational University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117576;
  3. cInstitute of High Performance Computing, Agency for Science, Technology, and Research, Singapore 138632;
  4. dLaboratoire Matière et Systèmes Complexes (MSC), Centre National de la Recherche Scientifique Unité Mixte de Recherche 7057, Université Paris Diderot, F-75205 Paris cedex 13, France;
  5. eEngineering Department, University of Cambridge, Cambridge CB2 1PZ, United Kingdom; and
  6. fDivision of Bioengineering and
  7. gDepartment of Mechanical Engineering, National University of Singapore, Singapore 117576

  1. Edited by David A. Weitz, Harvard University, Cambridge, MA, and approved June 25, 2012 (received for review November 28, 2011)

Abstract

The role of geometrical confinement on collective cell migration has been recognized but has not been elucidated yet. Here, we show that the geometrical properties of the environment regulate the formation of collective cell migration patterns through cell–cell interactions. Using microfabrication techniques to allow epithelial cell sheets to migrate into strips whose width was varied from one up to several cell diameters, we identified the modes of collective migration in response to geometrical constraints. We observed that a decrease in the width of the strips is accompanied by an overall increase in the speed of the migrating cell sheet. Moreover, large-scale vortices over tens of cell lengths appeared in the wide strips whereas a contraction-elongation type of motion is observed in the narrow strips. Velocity fields and traction force signatures within the cellular population revealed migration modes with alternative pulling and/or pushing mechanisms that depend on extrinsic constraints. Force transmission through intercellular contacts plays a key role in this process because the disruption of cell–cell junctions abolishes directed collective migration and passive cell–cell adhesions tend to move the cells uniformly together independent of the geometry. Altogether, these findings not only demonstrate the existence of patterns of collective cell migration depending on external constraints but also provide a mechanical explanation for how large-scale interactions through cell–cell junctions can feed back to regulate the organization of migrating tissues.

Footnotes

  • ↵1S.R.K.V. and M.C.L. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. E-mail: ctlim{at}nus.edu.sg or benoit.ladoux{at}univ-paris-diderot.fr.

  • Author contributions: S.R.K.V., C.T.L., and B.L. designed research; S.R.K.V., M.C.L., T.L., A.J.K., and B.L. performed research; S.R.K.V., M.C.L., T.L., A.J.K., and B.L. contributed new reagents/analytic tools; S.R.K.V., M.C.L., T.L., P.H., A.J.K., C.T.L., and B.L. analyzed data; and S.R.K.V., M.C.L., C.T.L., and B.L. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1119313109/-/DCSupplemental.

Freely available online through the PNAS open access option.

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