Publication: Computational insights into the influence of substrate stiffness on collective cell migration
Loading...
Identifiers
Publication date
2020-10
Defense date
Advisors
Tutors
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Impact
Export
Abstract
Critically 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.
Description
Keywords
Cell polarisation, Collective cell migration, Continuum model, Finite element method, Stiffness gradient
Bibliographic citation
Garcia-Gonzalez, D. & Muñoz-Barrutia, A. (2020). Computational insights into the influence of substrate stiffness on collective cell migration. Extreme Mechanics Letters, 40, 100928.