Abstract
The ability of cells to follow gradients of extracellular matrix stiffness-durotaxis-has been implicated in development, fibrosis, and cancer. Here, we found multicellular clusters that exhibited durotaxis even if isolated constituent cells did not. This emergent mode of directed collective cell migration applied to a variety of epithelial cell types, required the action of myosin motors, and originated from supracellular transmission of contractile physical forces. To explain the observed phenomenology, we developed a generalized clutch model in which local stick-slip dynamics of cell-matrix adhesions was integrated to the tissue level through cell-cell junctions. Collective durotaxis is far more efficient than single-cell durotaxis; it thus emerges as a robust mechanism to direct cell migration during development, wound healing, and collective cancer cell invasion.
| Original language | English |
|---|---|
| Pages (from-to) | 1157-1161 |
| Number of pages | 5 |
| Journal | Science |
| Volume | 353 |
| Issue number | 6304 |
| DOIs | |
| Publication status | Published - 9 Sept 2016 |
| Externally published | Yes |
Funding
The authors acknowledge X. Serra-Picamal, V. Romaric, R. Alert, J. Cadademunt, and all members of the X.T. and P.R.-C. laboratories for stimulating discussions; N. Castro for technical assistance; and G. Charras, G. Scita, and E. Sahai for providing cells. This work was supported by the Spanish Ministry of Economy and Competitiveness (BFU2015-65074-P to X.T., BFU2011-23111 and BFU2014-52586-REDT to P.R.-C., DPI2015-64221-C2-1-R to J.M.G.-A., DPI2013-43727-R to J.J.M., PI14/00280 to D.N., RYC-2014-15559 to V.C., FPI BES-2013-063684 to J.E., IJCI-2014-19156 to A.E.-A., and IJCI-2014-19843 to A.L.), the Generalitat de Catalunya (2014-SGR-927), the European Research Council (CoG-616480 to X.T. and StG 306571 to J.M.G.-A.), Obra Social "La Caixa," Marie-Curie Action (CAFFORCE 328664 to A.L.), EMBO Long-Term Fellowship (EMBO ALTF 1235-2012 to A.L.), a Career Integration Grant within the seventh European Community Framework Programme (PCIG10-GA-2011-303848 to P.R.-C.), and Fundacio la Marato de TV3 (project 20133330 to P.R.-C.).
