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

Posa, Francesca and Grab, Anna Luise and Martin, Volker and Hose, Dirk and Seckinger, Anja and Mori, Giorgio and Vukičević, Slobodan and Cavalcanti-Adam, Elisabetta Ada (2019) Copresentation of BMP-6 and RGD ligands enhances cell adhesion and BMP-mediated signaling. Cells, 8 (12). ISSN 2073-4409

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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.

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