Abstract
Heparin-protein interactions are important in many physiological processes including angiogenesis, the growth of new blood vessels from existing ones. We have previously developed a highly angiogenic self-assembling gel, wherein the self-assembly process is triggered by the interactions between heparin and peptide amphiphiles (PAs) with a consensus heparin binding sequence. In this report, this consensus sequence was scrambled and incorporated into a new peptide amphiphile in order to study its importance in heparin interaction and bioactivity. Heparin was able to trigger gel formation of the scrambled peptide amphiphile (SPA). Furthermore, the affinity of the scrambled molecule for heparin was unchanged as shown by isothermal titration calorimetry and high Förster resonance emission transfer efficiency. However, both the mobile fraction and the dissociation rate constant of heparin, using fluorescence recovery after photobleaching, were markedly higher in its interaction with the scrambled molecule implying a weaker association. Importantly, the scrambled peptide amphiphile-heparin gel had significantly less angiogenic bioactivity as shown by decreased tubule formation of sandwiched endothelial cells. Hence, we believe that the presence of the consensus sequence stabilizes the interaction with heparin and is important for the bioactivity of these new materials.
Original language | English (US) |
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Pages (from-to) | 3298-3305 |
Number of pages | 8 |
Journal | Biomaterials |
Volume | 29 |
Issue number | 23 |
DOIs | |
State | Published - Aug 2008 |
Funding
This work was funded by the National Institutes of Health (1R01 EB003806-04) and the U.S. Army Telemedicine and Advanced Technology Research Center (TATRC W81XWH-05-1-0381). We thank Dr. B.M. Rabatic for performing the TEM, Dr. M.S. Rao for assistance with the CD and oscillating rheometry and Dr W. Lowe Jr. from the Department of Medicine at Northwestern University Feinberg School of Medicine, for donating the bPAEC. We also thank the following facilities at Northwestern University – the Biological Imaging Facility and the Cell Imaging Facility, the Keck Biophysics Facility, the Electron Probe Instrumentation Center, the Analytical Services Laboratory and Prof. W.R. Burghardt for use of the oscillating rheometer.
Keywords
- Angiogenesis
- Heparin
- Nanoparticle
- Self-assembly
ASJC Scopus subject areas
- Mechanics of Materials
- Ceramics and Composites
- Bioengineering
- Biophysics
- Biomaterials