title: Mixed Fibronectin-Derived Peptides Conjugated to a Chitosan Matrix Effectively Promotes Biological Activities through Integrins, α4β1, α5β1, αvβ3, and Syndecan.
abstract: Mimicking the biological function of the extracellular matrix is an approach to developing cell adhesive biomaterials. The RGD peptide, derived from fibronectin (Fn), mainly binds to integrin αvβ3 and has been widely used as a cell adhesive peptide on various biomaterials. However, cell adhesion to Fn is thought to be mediated by several integrin subtypes and syndecans. In this study, we synthesized an RGD-containing peptide (FIB1) and four integrin α4β1-binding-related motif-containing peptides (LDV, IDAPS, KLDAPT, and PRARI) and constructed peptide-chitosan matrices. The FIB1-chitosan matrix promoted human dermal fibroblast (HDF) attachment, and the C-terminal elongated PRARI (ePRARI-C)-conjugated chitosan matrix significantly promoted HDF attachment through integrin α4β1 and syndecan binding. Next, we constructed a mixed ePRARI-C- and FIB1-chitosan matrix to develop a Fn mimetic biomaterial. The mixed ePRARI-C/FIB1-chitosan matrix promoted significantly better cell attachment and neurite outgrowth compared to those of either ePRARI-C- or FIB1-chitosan matrices. HDF adhesion to the ePRARI-C/FIB1-chitosan matrix was mediated by integrin, α4β1, α5β1, and αvβ3, similar to HDF adhesion to Fn. These data suggest that an ePRARI-C/FIB1-chitosan matrix can be used as a tool to analyze the multiple functions of Fn and can serve as a Fn-mimetic biomaterial.
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hozumi
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Kyotaro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Haruna
authors.initials: H
authors.lastname: Hori
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Mari
authors.initials: M
authors.lastname: Miyagi
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Rika
authors.initials: R
authors.lastname: Nagao
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Keiko
authors.initials: K
authors.lastname: Takasaki
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kikkawa
authors.affiliation: Laboratory of Clinical Biochemistry, Department of Pharmacy, Tokyo University of Pharmacy and Life Sciences , Hachioji, Tokyo, Japan .
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
keywords: artificial extracellular matrix; cell adhesive peptide; chitosan; fibronectin; integrin