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Collective cell guidance by cooperative intercellular forces

2011; Nature Portfolio; Volume: 10; Issue: 6 Linguagem: Inglês

10.1038/nmat3025

1476-4660

Dhananjay T. Tambe, Corey Hardin, Thomas E. Angelini, K. Rajendran, Chan Young Park, Xavier Serra‐Picamal, Enhua H. Zhou, Muhammad H. Zaman, James P. Butler, David A. Weitz, Jeffrey J. Fredberg, Xavier Trepat,

Cancer Cells and Metastasis

Cells comprising a tissue migrate as part of a collective. How collective processes are coordinated over large multi-cellular assemblies has remained unclear, however, because mechanical stresses exerted at cell–cell junctions have not been accessible experimentally. We report here maps of these stresses within and between cells comprising a monolayer. Within the cell sheet there arise unanticipated fluctuations of mechanical stress that are severe, emerge spontaneously, and ripple across the monolayer. Within that stress landscape, local cellular migrations follow local orientations of maximal principal stress. Migrations of both endothelial and epithelial monolayers conform to this behaviour, as do breast cancer cell lines before but not after the epithelial–mesenchymal transition. Collective migration in these diverse systems is seen to be governed by a simple but unifying physiological principle: neighbouring cells join forces to transmit appreciable normal stress across the cell–cell junction, but migrate along orientations of minimal intercellular shear stress. The mechanical stresses within and between cells inside an advancing cellular monolayer are mapped experimentally. Cellular migration is found to be oriented in the direction of maximum principal stress indicating that cells collectively migrate to maintain minimal local intercellular shear stress.