Biomimetic peptides that engage specific integrin-dependent signaling pathways and bind to calcium phosphate surfaces.
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 alpha-helical structure or diminish its affinity for hydroxyapatite. Immobilized N15-PGRGDS bound MC3T3-E1 osteoblasts predominantly via the alpha v beta 3 integrin and induced focal adhesion kinase (FAK) phosphorylation at comparable levels to immobilized osteopontin. Immobilized N15-PDGEA bound MC3T3-E1 osteoblasts predominantly through the alpha 2 beta 1 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.
D000327:Adsorption; D040761:Biomimetic Materials / Q000378:metabolism*; D015153:Blotting, Western; D002130:Calcium Phosphates / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016023:Integrins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010455:Peptides / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D002130:Calcium Phosphates; D016023:Integrins; D010455:Peptides; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; C485829:calcium phosphate, dibasic, anhydrous