87635 20210902121604.0 doi 10.1371/journal.pone.0220019 sideral 115643 ART-2020-115643 eng Anguiano, María The use of mixed collagen-Matrigel matrices of increasing complexity recapitulates the biphasic role of cell adhesion in cancer cell migration: ECM sensing, remodeling and forces at the leading edge of cancer invasion 2020 Access copy available to the general public Unrestricted The migration of cancer cells is highly regulated by the biomechanical properties of their local microenvironment. Using 3D scaffolds of simple composition, several aspects of cancer cell mechanosensing (signal transduction, EMC remodeling, traction forces) have been separately analyzed in the context of cell migration. However, a combined study of these factors in 3D scaffolds that more closely resemble the complex microenvironment of the cancer ECM is still missing. Here, we present a comprehensive, quantitative analysis of the role of cell-ECM interactions in cancer cell migration within a highly physiological environment consisting of mixed Matrigel-collagen hydrogel scaffolds of increasing complexity that mimic the tumor microenvironment at the leading edge of cancer invasion. We quantitatively show that the presence of Matrigel increases hydrogel stiffness, which promotes ß1 integrin expression and metalloproteinase activity in H1299 lung cancer cells. Then, we show that ECM remodeling activity causes matrix alignment and compaction that favors higher tractions exerted by the cells. However, these traction forces do not linearly translate into increased motility due to a biphasic role of cell adhesions in cell migration: at low concentration Matrigel promotes migration-effective tractions exerted through a high number of small sized focal adhesions. However, at high Matrigel concentration, traction forces are exerted through fewer, but larger focal adhesions that favor attachment yielding lower cell motility. info:eu-repo/grantAgreement/ES/MICINN/RTI2018-094494-B-C22 info:eu-repo/grantAgreement/ES/MINECO/BES-2013-064996 info:eu-repo/grantAgreement/ES/MINECO/BES-2016-076280 info:eu-repo/grantAgreement/ES/MINECO/DPI2015-64221-C2-1-R info:eu-repo/grantAgreement/ES/MINECO/DPI2015-64221-C2-2 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.24 2020 MULTIDISCIPLINARY SCIENCES 26 / 73 = 0.356 2020 Q2 T2 0.99 2020 Multidisciplinary 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Morales, Xabier Castilla, Carlos Rodríguez, Pena, Alejandro Ederra, Cristina Martínez, Martín Ariz, Mikel Esparza, Maider Amaveda, Hippolyte Universidad de Zaragoza (orcid)0000-0003-2212-447X Mora, Mario Universidad de Zaragoza (orcid)0000-0003-4747-7327 Movilla, Nieves Universidad de Zaragoza (orcid)0000-0002-0163-8378 García, Aznar, José Manuel Universidad de Zaragoza (orcid)0000-0002-9864-7683 Cortés-Domínguez, Iván Ortiz de Solorzano, Carlos 5004 X Universidad de Zaragoza Dpto. Ingeniería Mecánica Proy. investigacion HJA 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 5001 065 Universidad de Zaragoza Dpto. Ciencia Tecnol.Mater.Fl. Área Cienc.Mater. Ingen.Metal. 15, 1 (2020), e0220019 [29 pp.] PLoS One PloS one 1932-6203 5335576 http://zaguan.unizar.es/record/87635/files/texto_completo.pdf Versión publicada 488040 http://zaguan.unizar.es/record/87635/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:87635 articulos driver 2021-09-02-08:36:45 ARTICLE