title: Integrin-dependent cell behavior on ECM peptide-conjugated chitosan membranes.
abstract: Extracellular matrix (ECM) plays an important role in tissue regeneration by promoting cell adhesion, migration, proliferation, and differentiation. ECM mimetics are of importance for tissue engineering because of their functions as scaffolds for cells. Previously, we developed bioactive laminin-derived peptide-conjugated chitosan membranes and demonstrated their cell- and peptide-type specific functions. Here, we conjugated twelve integrin-binding peptides derived from ECM proteins onto chitosan membranes and examined biological activity. Seven peptide-chitosan membranes promoted human foreskin fibroblast attachment. Additionally, FIB1 (YAVTGRGDSPAS; from fibronectin), A99 (AGTFALRGDNPQG; from laminin alpha1 chain), EF1zz (ATLQLQEGRLHFXFDLGKGR, X = Nle; from laminin alpha1 chain), and 531 (GEFYFDLRLKGDKY; from collagen alpha1 (IV) chain) conjugated chitosan membranes promoted integrin-dependent cell adhesion. Various integrins, including alphav, beta1, and beta3, were involved in the cell adhesion to the peptide-chitosan membranes. Further, only the FIB1- and A99-chitosan membranes promoted neurite outgrowth with PC12 rat pheochromocytoma cells. These data demonstrate that peptide-chitosan membranes can regulate specific integrin-mediated cell responses and are useful constructs as ECM mimetics.
authors.affiliation: Laboratory of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Natsumi
authors.initials: N
authors.lastname: Yamagata
authors.forename: Deborah
authors.initials: D
authors.lastname: Philp
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hozumi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kadoya
authors.forename: Hynda K
authors.initials: HK
authors.lastname: Kleinman
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D004492:Edetic Acid / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology / Q000648:ultrastructure; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry; D051381:Rats
chemical_list: D000199:Actins; D016326:Extracellular Matrix Proteins; D016023:Integrins; D008567:Membranes, Artificial; D010455:Peptides; D006493:Heparin; D048271:Chitosan; D004492:Edetic Acid