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Biomimetic peptides that engage specific integrin‐dependent signaling pathways and bind to calcium phosphate surfaces
Author(s) -
Gilbert Michele,
Giachelli Cecilia M.,
Stayton Patrick S.
Publication year - 2003
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.10053
Subject(s) - integrin , phosphorylation , osteopontin , focal adhesion , microbiology and biotechnology , adhesion , peptide , signal transduction , cell adhesion , biochemistry , materials science , biophysics , receptor , chemistry , biology , cell , immunology , composite material
Abstract Many important matrix proteins involved in bone remodeling contain separate domains that orient the protein on hydroxyapatite and interact with target cell receptors, respectively. We have designed two synthetic peptides that mimic the dual activities of these large, complex proteins by binding to calcium phosphate minerals and by engaging integrin‐dependent signaling pathways in osteoblasts. The addition of either PGRGDS from osteopontin or PDGEA from collagen type I to the HAP‐binding domain of statherin (N15 domain) did not alter its α‐helical structure or diminish its affinity for hydroxyapatite. Immobilized N15‐PGRGDS bound MC3T3‐E1 osteoblasts predominantly via the αvβ3 integrin and induced focal adhesion kinase (FAK) phosphorylation at comparable levels to immobilized osteopontin. Immobilized N15‐PDGEA bound MC3T3‐E1 osteoblasts predominantly through the α2β1 integrin and induced similar levels of FAK phosphorylation. Although both peptides induced FAK phosphorylation with similar time courses, only the N15‐PDGEA peptide induced ERK1/2 phosphorylation, showing that these peptides are also capable of engaging integrin‐specific signaling pathways. This peptide system can be used to study adhesion‐dependent control of signaling in the context of the relevant biomineral surface and may also be useful in biomaterial and tissue engineering applications. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 69–77, 2003