Abstract
Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.
Original language | English (US) |
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Pages (from-to) | 821-829 |
Number of pages | 9 |
Journal | Nature nanotechnology |
Volume | 12 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1 2017 |
Funding
The NIH National Institute of Dental and Craniofacial Research grant 5R01DE015920-10, and also by the Louis A. Simpson & KimberlyQuerrey Center for Regenerative Nanomedicine at Northwestern University. The synthesis and structural characterization of this work was supported by the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by DOE, Office of Science, Basic Energy Sciences, under award no. DE-SC0000989. Studies on the dynamics and X-ray scattering were supported by the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, under award no. DE-FG02-00ER45810. The SAXS experiments were performed at the DND-CAT located at Sector 5 of the Advanced Photon Source (APS). Synchrotron X-ray ìCT experiments were performed at Sector 2-BM of the APS.We thank the following facilities at Northwestern University: Analytical BioNanotechnology Equipment Core, Peptide Synthesis Core, Center for Advanced Microscopy, Biological Imaging Facility, Keck Biophysics Facility, Integrated Molecular Structure Education and Research Center, Quantitative Bio-element Imaging Center, Center for Advanced Molecular Imaging, and Research Histology and Phenotyping Laboratory.
ASJC Scopus subject areas
- Condensed Matter Physics
- Bioengineering
- Atomic and Molecular Physics, and Optics
- Electrical and Electronic Engineering
- Biomedical Engineering
- General Materials Science