García González, DanielMuñoz Barrutia, María Arrate2022-02-012022-02-012020-10Garcia-Gonzalez, D. & Muñoz-Barrutia, A. (2020). Computational insights into the influence of substrate stiffness on collective cell migration. Extreme Mechanics Letters, 40, 100928.2352-4316https://hdl.handle.net/10016/34002Critically 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.9eng© 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.Atribución-NoComercial-SinDerivadas 3.0 EspañaCell polarisationCollective cell migrationContinuum modelFinite element methodStiffness gradientresearch articleBiología y Biomedicinahttps://doi.org/10.1016/j.eml.2020.100928open access11009289Extreme Mechanics Letters40AR/0000027568