Stiffness-dependent active wetting enables optimal collective cell durotaxis

Autor: Macià Esteve Pallarès, Irina Pi-Jaumà, Isabela Corina Fortunato, Valeria Grazu, Manuel Gómez-González, Pere Roca-Cusachs, Jesus M. de la Fuente, Ricard Alert, Raimon Sunyer, Jaume Casademunt, Xavier Trepat
Přispěvatelé: Generalitat de Catalunya, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Diputación General de Aragón, European Commission, European Research Council, Fundació La Marató de TV3, Fundación 'la Caixa', Ministerio de Economía y Competitividad (España)
Rok vydání: 2022
Předmět:
Zdroj: Nature Physics.
ISSN: 1745-2481
1745-2473
Popis: The directed migration of cellular clusters enables morphogenesis, wound healing and collective cancer invasion. Gradients of substrate stiffness direct the migration of cellular clusters in a process called collective durotaxis, but the underlying mechanisms remain unclear. Here we unveil a connection between collective durotaxis and the wetting properties of cellular clusters. We show that clusters of cancer cells dewet soft substrates and wet stiff ones. At intermediate stiffness—at the crossover from low to high wettability—clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient and actomyosin activity. We demonstrate this behaviour on substrates coated with the cell–cell adhesion protein E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop an active wetting model that explains collective durotaxis in terms of a balance between in-plane active traction and tissue contractility and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a physical mechanism of collective durotaxis, through both cell–cell and cell–substrate adhesion ligands, based on the wetting properties of active droplets.
This paper was funded by the Generalitat de Catalunya (AGAUR SGR-2017-01602 to X.T., AGAUR SGR-2017-1061 to J.C., the CERCA Programme and ‘ICREA Academia’ awards to P.R.-C. and J.C.); the Spanish Ministry for Science and Innovation MICCINN/FEDER (PGC2018-099645-B-I00 to X.T., PID2019-110298GB-I00 to P.R.-C., PID2019-108842GB-C21 to J.C., RTI2018-101256-J-I00 and RYC2019-026721-I to R.S., FPU19/05492 to I.P.-J., FPU15/06516 to M.-E.P.); Fondo Social de la DGA (grupos DGA) to V.G. and J.M.d.l.F.; European Research Council (Adv-883739 to X.T.); Fundació la Marató de TV3 (project 201903-30-31-32 to X.T.); the European Commission (H2020-FETPROACT-01-2016-731957 to P.R.-C. and X.T.); the European Union’s Horizon 2020 research and innovation programme (under the Marie Skłodowska-Curie grant agreement no. 797621 to M.G.-G.); the European Foundation for the Study of Chronic Liver Failure (EF-Clif); and the La Caixa Foundation (LCF/PR/HR20/52400004 to P.R.-C. and X.T.). IBEC is the recipient of a Severo Ochoa Award of Excellence from MINECO. R.S. is a Serra Húnter fellow.
Databáze: OpenAIRE
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