Copresentation of BMP-6 and RGD ligands enhances cell adhesion and BMP-mediated signaling

• Verfasst von: Posa, Francesca [VerfasserIn]
• Verfasst von: Grab, Anna Luise [VerfasserIn]
• Verfasst von: Hose, Dirk [VerfasserIn]
• Verfasst von: Seckinger, Anja [VerfasserIn]
• Verfasst von: Cavalcanti-Adam, Elisabetta A. [VerfasserIn]
• Titel: Copresentation of BMP-6 and RGD ligands enhances cell adhesion and BMP-mediated signaling
• Verf.angabe: Francesca Posa, Anna Luise Grab, Volker Martin, Dirk Hose, Anja Seckinger, Giorgio Mori, Slobodan Vukicevic and Elisabetta Ada Cavalcanti-Adam
• E-Jahr: 2019
• Jahr: 15 December 2019
• Umfang: 16 S.
• Fussnoten: Gesehen am 19.02.2020
• Titel Quelle: Enthalten in: Cells
• Ort Quelle: Basel : MDPI, 2012
• Jahr Quelle: 2019
• Band/Heft Quelle: 8(2019,12) Artikel-Nummer 1646, 16 Seiten
• ISSN Quelle: 2073-4409
• DOI: doi:10.3390/cells8121646
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: BMP/Smad signaling
• Sach-SW: bone morphogenetic protein 6
• Sach-SW: integrin ligands
• Sach-SW: myotube formation
• Sach-SW: surface copresentation
• K10plus-PPN: 1690351659

Abstract

We report on the covalent immobilization of bone morphogenetic protein 6 (BMP-6) and its co-presentation with integrin ligands on a nanopatterned platform to study cell adhesion and signaling responses which regulate the transdifferentiation of myoblasts into osteogenic cells. To immobilize BMP-6, the heterobifunctional linker MU-NHS is coupled to amine residues of the growth factor; this prevents its internalization while ensuring that its biological activity is maintained. Additionally, to allow cells to adhere to such platform and study signaling events arising from the contact to the surface, we used click-chemistry to immobilize cyclic-RGD carrying an azido group reacting with PEG-alkyne spacers via copper-catalyzed 1,3-dipolar cycloaddition. We show that the copresentation of BMP-6 and RGD favors focal adhesion formation and promotes Smad 1/5/8 phosphorylation. When presented in low amounts, BMP-6 added to culture media of cells adhering to the RGD ligands is less effective than BMP-6 immobilized on the surfaces in inducing Smad complex activation and in inhibiting myotube formation. Our results suggest that a local control of ligand density and cell signaling is crucial for modulating cell response.