title: Topological Control of Extracellular Matrix Growth: A Native-Like Model for Cell Morphodynamics Studies.
abstract: The interaction of cells with their natural environment influences a large variety of cellular phenomena, including cell adhesion, proliferation, and migration. The complex extracellular matrix network has challenged the attempts to replicate in vitro the heterogeneity of the cell environment and has threatened, in general, the relevance of in vitro studies. In this work, we describe a new and extremely versatile approach to generate native-like extracellular matrices with controlled morphologies for the in vitro study of cellular processes. This general approach combines the confluent culture of fibroblasts with microfabricated guiding templates to direct the three-dimensional growth of well-defined extracellular networks which recapitulate the structural and biomolecular complexity of features typically found in vivo. To evaluate its performance, we studied fundamental cellular processes, including cell cytoskeleton organization, cell-matrix adhesion, proliferation, and protrusions morphodynamics. In all cases, we found striking differences depending on matrix architecture and, in particular, when compared to standard two-dimensional environments. We also assessed whether the engineered matrix networks influenced cell migration dynamics and locomotion strategy, finding enhanced migration efficiency for cells seeded on aligned matrices. Altogether, our methodology paves the way to the development of high-performance models of the extracellular matrix for potential applications in tissue engineering, diagnosis, or stem-cell biology.
authors.affiliation: Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC) , Baldiri Reixac 15-21, 08028 Barcelona, Spain.|Department of Engineering: Electronics, University of Barcelona , 08028 Barcelona, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.
authors.forename: David
authors.identifier: http://orcid.org/0000-0001-7930-2535
authors.initials: D
authors.lastname: Caballero
authors.affiliation: Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC) , Baldiri Reixac 15-21, 08028 Barcelona, Spain.|Department of Engineering: Electronics, University of Barcelona , 08028 Barcelona, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Samitier
keywords: biomimetics; cell migration; engineered cell-derived matrices; extracellular matrix; in vitro model