title: Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility.
abstract: The nanostructures of self-assembling biomaterials have been previously designed to tune the release of growth factors in order to optimize biological repair and regeneration. We report here on the discovery that weakly cohesive peptide nanostructures in terms of intermolecular hydrogen bonding, when combined with low concentrations of osteogenic growth factor, enhance both BMP-2 and Wnt mediated signaling in myoblasts and bone marrow stromal cells, respectively. Conversely, analogous nanostructures with enhanced levels of internal hydrogen bonding and cohesion lead to an overall reduction in BMP-2 signaling. We propose that the mechanism for enhanced growth factor signaling by the nanostructures is related to their ability to increase diffusion within membrane lipid rafts. The phenomenon reported here could lead to new nanomedicine strategies to mediate growth factor signaling for translational targets.
authors.affiliation: Department of Materials Science and Engineering Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Newcomb
authors.affiliation: Department of Materials Science and Engineering Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Shantanu
authors.initials: S
authors.lastname: Sur
authors.affiliation: Department of Materials Science and Engineering Northwestern University , Evanston, Illinois 60208, United States.
authors.forename: Sungsoo S
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Simpson Querrey Institute for BioNanotechnology, Northwestern University , Chicago, Illinois 60611, United States.
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Yu
authors.affiliation: Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry of USC, The University of Southern California , Los Angeles, California 90033, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry of USC, The University of Southern California , Los Angeles, California 90033, United States.
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
authors.affiliation: Department of Materials Science and Engineering Northwestern University , Evanston, Illinois 60208, United States.|Simpson Querrey Institute for BioNanotechnology, Northwestern University , Chicago, Illinois 60611, United States.|Department of Biomedical Engineering, Northwestern University , Evanston, Illinois 60208, United States.|Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.|Department of Medicine, Northwestern University , Chicago, Illinois 60611, United States.
authors.forename: Samuel I
authors.initials: SI
authors.lastname: Stupp
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D021962:Membrane Microdomains / Q000187:drug effects* / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry*; D010012:Osteogenesis; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D000072757:Protein Conformation, beta-Strand; D015398:Signal Transduction; D013499:Surface Properties
chemical_list: D055396:Bone Morphogenetic Protein 2; D010455:Peptides
keywords: BMP-2; LRAP; Self-assembly; growth factor signaling; lipid raft