title: Surface-Driven Collagen Self-Assembly Affects Early Osteogenic Stem Cell Signaling.
abstract: This study reports how extracellular matrix (ECM) ligand self-assembly on biomaterial surfaces and the resulting nanoscale architecture can drive stem cell behavior. To isolate the biological effects of surface wettability on protein deposition, folding, and ligand activity, a polydimethylsiloxane (PDMS)-based platform was developed and characterized with the ability to tune wettability of elastomeric substrates with otherwise equivalent topology, ligand loading, and mechanical properties. Using this platform, markedly different assembly of covalently bound type I collagen monomers was observed depending on wettability, with hydrophobic substrates yielding a relatively rough layer of collagen aggregates compared to a smooth collagen layer on more hydrophilic substrates. Cellular and molecular investigations with human bone marrow stromal cells revealed higher osteogenic differentiation and upregulation of focal adhesion-related components on the resulting smooth collagen layer coated substrates. The initial collagen assembly driven by the PDMS surface directly affected α1β1 integrin/discoidin domain receptor 1 signaling, activation of the extracellular signal-regulated kinase/mitogen activated protein kinase pathway, and ultimately markers of osteogenic stem cell differentiation. We demonstrate for the first time that surface-driven ligand assembly on material surfaces, even on materials with otherwise identical starting topographies and mechanical properties, can dominate the biomaterial surface-driven cell response.
authors.affiliation: Department of Orthopedics, Balgrist University Hospital, University of Zurich, Lengghalde 5, 8008, Zürich, Switzerland.|Laboratory for Orthopedic Biomechanics, ETH Zurich, Lengghalde 5, 8008, Zürich, Switzerland.
authors.forename: Tojo
authors.initials: T
authors.lastname: Razafiarison
authors.affiliation: Department of Orthopedics, Balgrist University Hospital, University of Zurich, Lengghalde 5, 8008, Zürich, Switzerland.|Laboratory for Orthopedic Biomechanics, ETH Zurich, Lengghalde 5, 8008, Zürich, Switzerland.
authors.forename: Unai
authors.initials: U
authors.lastname: Silván
authors.affiliation: Department of Orthopedics, Balgrist University Hospital, University of Zurich, Lengghalde 5, 8008, Zürich, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Meier
authors.affiliation: Department of Orthopedics, Balgrist University Hospital, University of Zurich, Lengghalde 5, 8008, Zürich, Switzerland.|Laboratory for Orthopedic Biomechanics, ETH Zurich, Lengghalde 5, 8008, Zürich, Switzerland.
authors.forename: Jess G
authors.initials: JG
authors.lastname: Snedeker
mesh_terms: D002454:Cell Differentiation; D003094:Collagen / Q000737:chemistry; D000070819:Discoidin Domain Receptor 1 / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D039222:Integrin alpha1beta1 / Q000096:biosynthesis; D010012:Osteogenesis; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D039222:Integrin alpha1beta1; D003094:Collagen; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1
keywords: collagen monomer; hydrophobicity; nanotopographical cue; polydimethylsiloxane; stem cell