{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T23:59:05Z","timestamp":1772236745709,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,15]],"date-time":"2019-12-15T00:00:00Z","timestamp":1576368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB TRR79 TP M09"],"award-info":[{"award-number":["SFB TRR79 TP M09"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB TRR79 TP B05"],"award-info":[{"award-number":["SFB TRR79 TP B05"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells8121646","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T05:19:38Z","timestamp":1576473578000},"page":"1646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Copresentation of BMP-6 and RGD Ligands Enhances Cell Adhesion and BMP-Mediated Signaling"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8099-3505","authenticated-orcid":false,"given":"Francesca","family":"Posa","sequence":"first","affiliation":[{"name":"Department of Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstr. 29, 69120 Heidelberg, Germany"},{"name":"Department of Biophysical Chemistry, Institute of Physical Chemistry, Heidelberg University, Im Neuenheimer Feld 253, 69120 Heidelberg, Germany"},{"name":"Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Luise","family":"Grab","sequence":"additional","affiliation":[{"name":"Department of Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstr. 29, 69120 Heidelberg, Germany"},{"name":"Department of Biophysical Chemistry, Institute of Physical Chemistry, Heidelberg University, Im Neuenheimer Feld 253, 69120 Heidelberg, Germany"},{"name":"Genome Biology Unit, EMBL, Meyerhofstra\u00dfe 1, 69117 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstr. 29, 69120 Heidelberg, Germany"},{"name":"Department of Biophysical Chemistry, Institute of Physical Chemistry, Heidelberg University, Im Neuenheimer Feld 253, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Hose","sequence":"additional","affiliation":[{"name":"Laboratory for Myeloma Research and Medical Clinic V, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Seckinger","sequence":"additional","affiliation":[{"name":"Laboratory for Myeloma Research and Medical Clinic V, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-0247","authenticated-orcid":false,"given":"Giorgio","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto, 71122 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4076-0285","authenticated-orcid":false,"given":"Slobodan","family":"Vukicevic","sequence":"additional","affiliation":[{"name":"Laboratory for Mineralized Tissues, Center for Translational and Clinical Research, School of Medicine, University of Zagreb, \u0160alata 11, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0243-1552","authenticated-orcid":false,"given":"Elisabetta Ada","family":"Cavalcanti-Adam","sequence":"additional","affiliation":[{"name":"Department of Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstr. 29, 69120 Heidelberg, Germany"},{"name":"Department of Biophysical Chemistry, Institute of Physical Chemistry, Heidelberg University, Im Neuenheimer Feld 253, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,15]]},"reference":[{"key":"ref_1","unstructured":"Wagner, D.O., Sieber, C., Bhushan, R., B\u00f6rgermann, J.H., Graf, D., and Knaus, P. 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