Collective cell durotaxis emerges from long-range intercellular force transmission.
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.
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
Raimon
R
Sunyer
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
Vito
V
Conte
Aragon Institute of Engineering Research (I3A), University of Zaragoza, 50018 Zaragoza, Spain.
Jorge
J
Escribano
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
Alberto
A
Elosegui-Artola
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
Anna
A
Labernadie
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
Léo
L
Valon
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain. University of Barcelona, 08028 Barcelona, Spain. Centro de Investigación Biomédica en Red en Enfermedades Respiratorias, 28029 Madrid, Spain.
Daniel
D
Navajas
Aragon Institute of Engineering Research (I3A), University of Zaragoza, 50018 Zaragoza, Spain.
José Manuel
JM
García-Aznar
Laboratory of Numerical Analysis (LaCàN), Polytechnic University of Catalonia (UPC- BarcelonaTech), 08036 Barcelona, Spain.
José J
JJ
Muñoz
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain. University of Barcelona, 08028 Barcelona, Spain. rocacusachs@ub.edu xtrepat@ibecbarcelona.eu.
Pere
P
Roca-Cusachs
Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain. University of Barcelona, 08028 Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, 28029 Madrid, Spain. rocacusachs@ub.edu xtrepat@ibecbarcelona.eu.
Xavier
X
Trepat
D002460:Cell Line; D004847:Epithelial Cells / Q000502:physiology*; D005109:Extracellular Matrix; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D008858:Microscopy, Phase-Contrast; D009218:Myosins / Q000502:physiology; D000071442:Taxis Response
D009218:Myosins