title: Reconstitution of laminin-111 biological activity using multiple peptide coupled to chitosan scaffolds.
abstract: Laminin-111, a multifunctional matrix protein, has diverse biological functions. Previously, we have identified various biologically active sequences in laminin-111 by a systematic peptide screening. We also demonstrated that peptide-conjugated chitosan matrices enhance the biological functions of the active sequences and are useful as a scaffold. Here, we conjugated sixty biologically active laminin-111 peptides onto chitosan matrices. The twenty-nine peptide-chitosan matrices promoted various biological activities, including cell attachment, spreading, and neurite outgrowth. The biological activities of peptide-chitosan matrices depend on the peptide. These peptide-chitosan matrices are categorized into six groups depending on their biological activities. Next, we conjugated five active peptides, which showed strong cell attachment activity in the each group, onto a single chitosan matrix to mimic the multiple activities of laminin-111. The mixed peptides-chitosan matrix significantly promoted cell attachment and cell spreading over that observed with the individual peptides. We also demonstrated that a mixed peptides-chitosan matrix, using four neurite outgrowth-promoting peptides each from a different group, enhanced the activity. These data suggest that the mixed peptides synergistically induce laminin-like biological activities on a chitosan matrix. The active peptides-chitosan matrices described here have potential for use as biomaterial for tissue engineering and regeneration.
authors.affiliation: Laboratory of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hozumi
authors.forename: Ayano
authors.initials: A
authors.lastname: Sasaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamada
authors.forename: Dai
authors.initials: D
authors.lastname: Otagiri
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Chikara
authors.initials: C
authors.lastname: Fujimori
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D016023:Integrins / Q000276:immunology; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D016596:Vinculin / Q000378:metabolism
chemical_list: D000199:Actins; D000906:Antibodies; D016023:Integrins; D007797:Laminin; D010455:Peptides; D016596:Vinculin; D006493:Heparin; D048271:Chitosan; D004492:Edetic Acid; D051416:Focal Adhesion Protein-Tyrosine Kinases