Adhesion modulates cell morphology and migration within dense fibrous networks

Abstract

One of the most fundamental abilities required for the sustainability of complex life forms is active cell migration, since it is essential in diverse processes from morphogenesis to leukocyte chemotaxis in immune response. The movement of a cell is the result of intricate mechanisms, that involve the coordination between mechanical forces, biochemical regulatory pathways and environmental cues. In particular, epithelial cancer cells have to employ mechanical strategies in order to migrate through the tissues basement membrane and infiltrate the bloodstream during the invasion stage of metastasis. In this work we explore how mechanical interactions such as spatial restriction and adhesion affect migration of a self-propelled droplet in dense fibrous media. We have performed a systematic analysis using a phase-field model and we propose a novel approach to simulate cell migration with Dissipative Particle Dynamics (DPD) modelling. With this purpose we have measured the cells velocity and quantified its morphology as a function of the fibre density and of its adhesiveness to the matrix fibres. Furthermore, we have compared our results to a previous in vitro migration assay of fibrosacorma cells in fibrous matrices. The results are model independent and show good agreement between the two methodologies and experiments in the literature, which indicates that these minimalist descriptions are able to capture the main features of the system. Our results indicate that adhesiveness is critical for cell migration, by modulating cell morphology in crowded environments and by enhancing cell velocity. In addition, our analysis suggests that matrix metalloproteinases (MMPs) play an important role as adhesiveness modulators. We propose that new assays should be carried out to address the role of adhesion and the effect of different MMPs in cell migration under confined conditions.