Copresentation of BMP-6 and RGD Ligands Enhances Cell Adhesion and BMP-Mediated Signaling

Autor:	Anja Seckinger, Giorgio Mori, Volker Martin, Anna Luise Grab, Elisabetta Ada Cavalcanti-Adam, Slobodan Vukicevic, Francesca Posa, Dirk Hose
Přispěvatelé:	Hematology, Basic (bio-) Medical Sciences
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Integrins Immobilized Proteins/chemistry Metal Nanoparticles Smad Proteins 02 engineering and technology SMAD Integrins/metabolism Ligands Myoblasts Osteogenesis Transforming Growth Factor beta Signal Transduction/drug effects Cell Adhesion/drug effects integrin ligands bone morphogenetic protein 6 surface copresentation myotube formation BMP/Smad signaling Internalization Smad Proteins/metabolism media_common biology Chemistry phosphorylation hematology Transdifferentiation Metal Nanoparticles/chemistry Cell Differentiation General Medicine 021001 nanoscience & nanotechnology 3. Good health Cell biology Osteogenesis/drug effects Bone morphogenetic protein 6 Gold/chemistry surface copresentation Phosphorylation 0210 nano-technology Oligopeptides Transforming Growth Factor beta/metabolism Signal Transduction Protein Binding Cell signaling mice Oligopeptides/chemistry media_common.quotation_subject Integrin bone morphogenetic protein 6 Article Cell Line 03 medical and health sciences integrin ligands Cell Adhesion Animals Bone Morphogenetic Protein 6/chemistry Cell adhesion BMP/Smad signaling 030104 developmental biology Immobilized Proteins myotube formation Cell Differentiation/drug effects biology.protein Gold Myoblasts/cytology
Zdroj:	Cells Volume 8 Issue 12
ISSN:	2073-4409
DOI:	10.3390/cells8121646
Popis:	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.
Databáze:	OpenAIRE
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