title: Role of material-driven fibronectin fibrillogenesis in cell differentiation.
abstract: Fibronectin (FN) is a ubiquitous extracellular matrix protein (ECM) protein that is organized into fibrillar networks by cells through an integrin-mediated process that involves contractile forces. This assembly allows for the unfolding of the FN molecule, exposing cryptic domains that are not available in the native globular FN structure and activating intracellular signalling complexes. However, organization of FN into a physiological fibrillar network upon adsorption on a material surface has not been observed. Here we demonstrate cell-free, material-induced FN fibrillogenesis into a biological matrix with enhanced cellular activities. We found that simple FN adsorption onto poly(ethyl acrylate) surfaces, but not control polymers, triggered FN organization into a fibrillar network via interactions in the amino-terminal 70 kDa fragment, which is involved in the formation of cell-mediated FN fibrils. Moreover, the material-driven FN fibrils exhibited enhanced biological activities in terms of myogenic differentiation compared to individual FN molecules and even type I collagen. Our results demonstrate that molecular assembly of FN can take place at the material interface, giving rise to a physiological protein network similar to fibrillar matrices assembled by cells. This research identifies material surfaces that trigger the organization of extracellular matrix proteins into biological active fibrils and establishes a new paradigm to engineer ECM-mimetic biomaterials.
authors.affiliation: Center for Biomaterials and Tissue Engineering, Universidad Politécnica de Valencia, Spain. masalsan@fis.upv.es
authors.forename: Manuel
authors.initials: M
authors.lastname: Salmerón-Sánchez
authors.forename: Patricia
authors.initials: P
authors.lastname: Rico
authors.forename: David
authors.initials: D
authors.lastname: Moratal
authors.forename: Ted T
authors.initials: TT
authors.lastname: Lee
authors.forename: Jean E
authors.initials: JE
authors.lastname: Schwarzbauer
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001843:Bone Cements / Q000737:chemistry; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D018625:Microscopy, Atomic Force; D019904:Polymethyl Methacrylate / Q000737:chemistry; D013499:Surface Properties
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; D001843:Bone Cements; D005353:Fibronectins; D016023:Integrins; C478961:poly(ethylacrylate); D019904:Polymethyl Methacrylate; D051416:Focal Adhesion Protein-Tyrosine Kinases