000087635 001__ 87635 000087635 005__ 20210902121604.0 000087635 0247_ $$2doi$$a10.1371/journal.pone.0220019 000087635 0248_ $$2sideral$$a115643 000087635 037__ $$aART-2020-115643 000087635 041__ $$aeng 000087635 100__ $$aAnguiano, María 000087635 245__ $$aThe 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 000087635 260__ $$c2020 000087635 5060_ $$aAccess copy available to the general public$$fUnrestricted 000087635 5203_ $$aThe 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. 000087635 536__ $$9info:eu-repo/grantAgreement/ES/MICINN/RTI2018-094494-B-C22$$9info:eu-repo/grantAgreement/ES/MINECO/BES-2013-064996$$9info:eu-repo/grantAgreement/ES/MINECO/BES-2016-076280$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2015-64221-C2-1-R$$9info:eu-repo/grantAgreement/ES/MINECO/DPI2015-64221-C2-2 000087635 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000087635 590__ $$a3.24$$b2020 000087635 591__ $$aMULTIDISCIPLINARY SCIENCES$$b26 / 73 = 0.356$$c2020$$dQ2$$eT2 000087635 592__ $$a0.99$$b2020 000087635 593__ $$aMultidisciplinary$$c2020$$dQ1 000087635 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000087635 700__ $$aMorales, Xabier 000087635 700__ $$aCastilla, Carlos 000087635 700__ $$aRodríguez, Pena, Alejandro 000087635 700__ $$aEderra, Cristina 000087635 700__ $$aMartínez, Martín 000087635 700__ $$aAriz, Mikel 000087635 700__ $$aEsparza, Maider 000087635 700__ $$0(orcid)0000-0003-2212-447X$$aAmaveda, Hippolyte$$uUniversidad de Zaragoza 000087635 700__ $$0(orcid)0000-0003-4747-7327$$aMora, Mario$$uUniversidad de Zaragoza 000087635 700__ $$0(orcid)0000-0002-0163-8378$$aMovilla, Nieves$$uUniversidad de Zaragoza 000087635 700__ $$0(orcid)0000-0002-9864-7683$$aGarcía, Aznar, José Manuel$$uUniversidad de Zaragoza 000087635 700__ $$aCortés-Domínguez, Iván 000087635 700__ $$aOrtiz de Solorzano, Carlos 000087635 7102_ $$15004$$2X$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cProy. investigacion HJA 000087635 7102_ $$15004$$2605$$aUniversidad de Zaragoza$$bDpto. Ingeniería Mecánica$$cÁrea Mec.Med.Cont. y Teor.Est. 000087635 7102_ $$15001$$2065$$aUniversidad de Zaragoza$$bDpto. Ciencia Tecnol.Mater.Fl.$$cÁrea Cienc.Mater. Ingen.Metal. 000087635 773__ $$g15, 1 (2020), e0220019 [29 pp.]$$pPLoS One$$tPloS one$$x1932-6203 000087635 8564_ $$s5335576$$uhttps://zaguan.unizar.es/record/87635/files/texto_completo.pdf$$yVersión publicada 000087635 8564_ $$s488040$$uhttps://zaguan.unizar.es/record/87635/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000087635 909CO $$ooai:zaguan.unizar.es:87635$$particulos$$pdriver 000087635 951__ $$a2021-09-02-08:36:45 000087635 980__ $$aARTICLE