Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates

doi:10.1073/pnas.0702259104

Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates

*Laboratoire Matière et Systèmes Complexes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7057, Batiment Condorcet, Université Paris 7, 10, rue Alice Domon et Léonie Duquet, F-75205 Paris Cedex 13, France; and
^†Physico-Chimie Curie, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 168, Institut Curie, 26, rue d'Ulm, F-75248 Paris Cedex 05, France

Communicated by Pierre-Gilles de Gennes, Collège de France, Paris, France, March 19, 2007 (received for review November 15, 2006)

Abstract

The physical properties of the cellular environment are involved in regulating the formation and maintenance of tissues. In particular, substrate rigidity appears to be a key factor dictating cell response on culture surfaces. Here we study the behavior of epithelial cells cultured on microfabricated substrates engineered to exhibit an anisotropic stiffness. The substrate consists of a dense array of micropillars of oval cross-section, so that one direction is made stiffer than the other. We demonstrate how such an anisotropic rigidity can induce directional epithelial growth and guide cell migration along the direction of greatest rigidity. Regions of high tractional stress and large cellular deformations within the sheets of cells are concentrated at the edges, in particular at the two poles of the islands along their long axis, in correlation with the orientation of actin stress fibers and focal adhesions. By inducing scattering activity of epithelial cells, we show that isolated cells also migrate along the direction of greatest stiffness. Taken together, these findings show that the mechanical interactions of cells with their microenvironment can be tuned to engineer particular tissue properties.

Footnotes

^‡To whom correspondence should be addressed. E-mail: benoit.ladoux{at}univ-paris-diderot.fr
Author contributions: A.B., P.S., and B.L. designed research; A.S., M.G., A.B., P.S., and B.L. performed research; A.S., M.G., A.B., P.S., and B.L. contributed new reagents/analytic tools; A.S., A.B., P.S., and B.L. analyzed data; and B.L. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0702259104/DC1.
Abbreviations:

ECM,

extracellular matrix;

MDCK,

Madin–Darby canine kidney;

PDMS,

polydimethylsiloxane;

PS,

polystyrene.