by Keyword: Anisotropy
Almici, Enrico, Caballero, David, Montero, Joan, Samitier, Josep, (2020). Engineering cell-derived matrices with controlled 3D architectures for pathophysiological studies Methods in Cell Biology (ed. Caballero, David, Kundu, Subhas C., Reis, Rui Luís), Academic Press (Cambridge, USA) 156, 161-183
The composition and architecture of the extracellular matrix (ECM) and their dynamic alterations, play an important regulatory role on numerous cellular processes. Cells embedded in 3D scaffolds show phenotypes and morphodynamics reminiscent of the native scenario. This is in contrast to flat environments, where cells display artificial phenotypes. The structural and biomolecular properties of the ECM are critical in regulating cell behavior via mechanical, chemical and topological cues, which induce cytoskeleton rearrangement and gene expression. Indeed, distinct ECM architectures are encountered in the native stroma, which depend on tissue type and function. For instance, anisotropic geometries are associated with ECM degradation and remodeling during tumor progression, favoring tumor cell invasion. Overall, the development of innovative in vitro ECM models of the ECM that reproduce the structural and physicochemical properties of the native scenario is of upmost importance to investigate the mechanistic determinants of tumor dissemination. In this chapter, we describe an extremely versatile technique to engineer three-dimensional (3D) matrices with controlled architectures for the study of pathophysiological processes in vitro. To this aim, a confluent culture of “sacrificial” fibroblasts was seeded on top of microfabricated guiding templates to induce the 3D ECM growth with specific isotropic or anisotropic architectures. The resulting matrices, and cells seeded on them, recapitulated the structure, composition, phenotypes and morphodynamics typically found in the native scenario. Overall, this method paves the way for the development of in vitro ECMs for pathophysiological studies with potential clinical relevance.
JTD Keywords: Extracellular matrix, Cell-derived matrix, 3D model, Biomimicry, Anisotropy
Caballero, D., Palacios, L., Freitas, P. P., Samitier, J., (2017). An interplay between matrix anisotropy and actomyosin contractility regulates 3D-directed cell migration Advanced Functional Materials 27, (35), 1702322
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.
JTD Keywords: Anisotropy, Directed cell migration, Extracellular matrices, Migration modes, Three dimensional microenvironments