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Computational insights into the influence of substrate stiffness on collective cell migration

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dc.affiliation.dptoUC3M. Departamento de Mecánica de Medios Continuos y Teoría de Estructurases
dc.affiliation.dptoUC3M. Departamento de Bioingenieríaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: Dinámica y Fractura de Elementos Estructuraleses
dc.affiliation.grupoinvUC3M. Grupo de Investigación: BSEL - Laboratorio de Ciencia e Ingeniería Biomédicaes
dc.contributor.authorGarcía González, Daniel
dc.contributor.authorMuñoz Barrutia, María Arrate
dc.contributor.funderComunidad de Madrides
dc.contributor.funderMinisterio de Economía y Competitividad (España)en
dc.date.accessioned2022-02-01T09:45:07Z
dc.date.available2022-02-01T09:45:07Z
dc.date.issued2020-10
dc.description.abstractCritically important biological phenomena in health and disease, such as wound healing, cancer metastasis, and embryonic development, are governed by collective cell migration. This highly complex process depends not only on cellular features, but also on different stimuli from the local cell environment. Cell migration is promoted by the combination of physico-chemical cues, including the mechanical properties of the extracellular matrix (ECM). Stiffness gradients within ECM have recently been demonstrated to result into preferred directions of cell migration. However, the specific mechanisms driving this directed collective cell migration and their relative roles remain unclear. Here, we develop a continuum formulation and its finite element (FE) implementation to test different hypotheses on the cause of spatial heterogeneities during cell migration on heterogeneous-stiffness substrates. We evaluate two key hypotheses: (i) cell polarisation is promoted by stiffness gradients within the ECM and; (ii) propulsion forces are weighted by ECM stiffness. Ultimately, we provide a robust in silico framework to explain experimental observations and guide future research.en
dc.description.sponsorshipThe authors thank Denis Wirtz (Johns Hopkins University) for relevant discussion. The authors acknowledge support from Programa de Apoyo a la Realizacion de Proyectos Interdiscisplinares de I+D para Jovenes Investigadores de la Universidad Carlos III de Madrid and Comunidad de Madrid, Spain (project: BIOMASKIN). DGG acknowledges support from the Talent Attraction grant, Spain (CM 2018 - 2018-T2/IND-9992) from the Comunidad de Madrid. This work was partially funded by projects TEC2015-73064-EXP and TEC2016-78052-R from the Spanish Ministry of Economy and a 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation, Spain.en
dc.format.extent9
dc.identifier.bibliographicCitationGarcia-Gonzalez, D. & Muñoz-Barrutia, A. (2020). Computational insights into the influence of substrate stiffness on collective cell migration. Extreme Mechanics Letters, 40, 100928.en
dc.identifier.doihttps://doi.org/10.1016/j.eml.2020.100928
dc.identifier.issn2352-4316
dc.identifier.publicationfirstpage1
dc.identifier.publicationissue100928
dc.identifier.publicationlastpage9
dc.identifier.publicationtitleExtreme Mechanics Lettersen
dc.identifier.publicationvolume40
dc.identifier.urihttps://hdl.handle.net/10016/34002
dc.identifier.uxxiAR/0000027568
dc.language.isoengen
dc.publisherElsevieren
dc.relation.projectIDGobierno de España. TEC2016-78052-Res
dc.relation.projectIDGobierno de España. TEC2015-73064-EXPes
dc.relation.projectIDComunidad de Madrid. BIOMASKIN-CM-UM3Mes
dc.relation.projectIDComunidad de Madrid. 2018-T2/IND-9992es
dc.rights© 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.en
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.accessRightsopen accessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subject.ecienciaBiología y Biomedicinaes
dc.subject.otherCell polarisationen
dc.subject.otherCollective cell migrationen
dc.subject.otherContinuum modelen
dc.subject.otherFinite element methoden
dc.subject.otherStiffness gradienten
dc.titleComputational insights into the influence of substrate stiffness on collective cell migrationen
dc.typeresearch article*
dc.type.hasVersionVoR*
dspace.entity.typePublication
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