title: Recombinant fibronectin matrix mimetics specify integrin adhesion and extracellular matrix assembly.
abstract: Tissue engineering seeks to create functional tissues and organs by integrating natural or synthetic scaffolds with bioactive factors and cells. Creating biologically active scaffolds that support key aspects of tissue regeneration, including the re-establishment of a functional extracellular matrix (ECM), is a challenge currently facing this field. During tissue repair, fibronectin is converted from an inactive soluble form into biologically active ECM fibrils through a cell-dependent process. ECM fibronectin promotes cell processes critical to tissue regeneration and regulates the deposition and organization of other ECM proteins. We previously developed biomimetics of ECM fibronectin by directly coupling the heparin-binding fragment of the first type III repeat of fibronectin (FNIII1H) to the integrin-binding repeats (FNIII8-10). As adhesive substrates, fibronectin matrix mimetics promote cell growth, migration, and contractility through a FNIII1H-dependent mechanism. Here, we analyzed fibronectin matrix mimetic variants designed to include all or part of the integrin-binding domain for their ability to support new ECM assembly. We found that specific modifications of the integrin-binding domain produced adhesive substrates that selectively engage different integrin receptors to, in turn, regulate the amount of fibronectin and collagen deposited into the ECM. The ability of fibronectin matrix mimetics to direct cell-substrate interactions and regulate ECM assembly makes them promising candidates for use as bioactive surfaces, where precise control over integrin-binding specificity and ECM deposition are required.
authors.affiliation: Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Roy
authors.forename: Denise C
authors.initials: DC
authors.lastname: Hocking
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins; D016023:Integrins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D011994:Recombinant Proteins