3 years ago

An Interplay between Matrix Anisotropy and Actomyosin Contractility Regulates 3D-Directed Cell Migration

An Interplay between Matrix Anisotropy and Actomyosin Contractility Regulates 3D-Directed Cell Migration
David Caballero, Josep Samitier, Paulo P. Freitas, Lucas Palacios
Directed cell migration is essential for many biological processes, such as embryonic development or cancer progression. Cell contractility and adhesion to the extracellular matrix are known to regulate cell locomotion machinery. However, the cross-talk between extrinsic and intrinsic factors at the molecular level on the biophysical mechanism of three dimensional (3D)-directed cell migration is still unclear. In this work, a novel physiologically relevant in vitro model of the extracellular microenvironment is used to reveal how the topological anisotropy of the extracellular matrix synergizes with actomyosin contractility to modulate directional cell migration morphodynamics. This study shows that cells seeded on polarized 3D matrices display asymmetric protrusion morphodynamics and in-vivo-like phenotypes. It is found that matrix anisotropy significantly enhances cell directionality, but strikingly, not the invasion distance of cells. In Rho-inhibited cells, matrix anisotropy counteracts the lack of actomyosin-driven forces to stabilize cell directionality suggesting a myosin-II-independent mechanism for cell guidance. Finally, this study shows that on isotropic 3D environments, cell directionality is independent of actomyosin contractility. Altogether, this study provides novel quantitative data on the biomechanical regulation of directional cell motion and shows the important regulatory role of matrix anisotropy and actomyosin forces to guide cell migration in 3D microenvironments. This work describes the generation of anisotropic cell-derived matrices for the study of physiopathological processes. Microfabricated guiding templates are combined with the confluent culture of fibroblasts to generate native-like 3D matrices with controlled architectures. This extracellular matrix model is allowed to unravel the critical interplay between matrix anisotropy with actomyosin contractility during directed 3D cell migration by modulating the locomotion strategy of cells.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201702322

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