Multifunctional hybrid networks based on self assembling peptide sequences
Author(s) | Sathaye, Sameer | |
Date Accessioned | 2014-12-03T16:03:19Z | |
Date Available | 2014-12-03T16:03:19Z | |
Publication Date | 2014 | |
Abstract | The overall aim of this dissertation is to achieve a comprehensive correlation between the molecular level changes in primary amino acid sequences of amphiphilic ?-hairpin peptides and their consequent solution-assembly properties and bulk network hydrogel behavior. This has been accomplished using two broad approaches. In the first approach, amino acid substitutions were made to peptide sequence MAX1 such that the hydrophobic surfaces of the folded ?-hairpins from the peptides demonstrate shape specificity in hydrophobic interactions with other ?-hairpins during the assembly process, thereby causing changes to the peptide nanostructure and bulk rheological properties of hydrogels formed from the peptides. Steric lock and key complementary hydrophobic interactions were designed to occur between two ?-hairpin molecules of a single molecule, LNK1 during ?-sheet fibrillar assembly of LNK1. Experimental results from circular dichroism, transmission electron microscopy and oscillatory rheology collectively indicate that the molecular design of the LNK1 peptide can be assigned the cause of the drastically different behavior of the networks relative to MAX1. The results indicate elimination or significant reduction of fibrillar branching due to steric complementarity in LNK1 that does not exist in MAX1, thus supporting the original hypothesis. As an extension of the designed steric lock and key complementarity between two ?-hairpin molecules of the same peptide molecule. LNK1, three new pairs of peptide molecules LP1-KP1, LP2-KP2 and LP3-KP3 that resemble complementary 'wedge' and 'trough' shapes when folded into ?-hairpins were designed and studied. All six peptides individually and when blended with their corresponding shape complement formed fibrillar nanostructures with non-uniform thickness values. Loose packing in the assembled structures was observed in all the new peptides as compared to the uniform tight packing in MAX1 by SANS analysis. This loose packing can be attributed to the designed wedge and trough shapes of the peptides disturbing formation of a uniform bilayer type structure proposed in the case of MAX1 with each hairpin having a flat hydrophobic surface. Although designed changes in hydrophobic shape of the peptide nanofibril core in the new peptides were found to significantly influence the self-assembled nanostructure and network rheological behavior, a lack of direct morphological and rheological evidence to prove shape specific hydrophobic interactions between wedge and trough shaped ?-hairpins was encountered. In the second approach, peptides with established differences in assembly kinetics and bulk mechanical properties of assembled peptide hydrogels were used to develop composite materials with diverse morphological and mechanical properties by blending with the biopolymer hyaluronic acid. The diverse properties of the composites have been correlated to the specific peptide hydrogels used to develop the composite and the different stages of peptide assembly at which blending with hyaluronic acid was carried out. Finally along with overall conclusions, the new area of co-assembly of peptides in solution has been explored and discussed as potential future work following the research discussed in this dissertation. Strategies such as construction of composite hydrogels from blends of MAX1/MAX8 peptide hydrogels and biologically important anionic species such as heparin biopolymer and DNA have been discussed. Another area of future work discussed is the design and study of peptides that can incorporate chemically crosslinkable functional groups in their hydrophobic amino acid side chains that can be covalently crosslinked after peptide assembly into fibrils. Such covalent crosslinking can potentially lead to stiffer individual peptide fibrils due to additional bond formation at the fibrillar core and therefore much stiffer hydrogels due to a synergistic effect. These enhanced stiffness values can render these new hydrogels excellent candidates for applications like development of extracellular mimetic materials and substrates with easily tunable stiffness values for stem cell differentiation studies. | en_US |
Advisor | Pochan, Darrin J. | |
Degree | Ph.D. | |
Department | University of Delaware, Department of Materials Science & Engineering | |
DOI | https://doi.org/10.58088/pytf-tq76 | |
Unique Identifier | 897367095 | |
URL | http://udspace.udel.edu/handle/19716/13416 | |
Publisher | University of Delaware | en_US |
URI | http://search.proquest.com/docview/1564480780?accountid=10457 | |
dc.subject.lcsh | Peptides. | |
dc.subject.lcsh | Self-assembly (Chemistry) | |
dc.subject.lcsh | Colloids. | |
dc.subject.lcsh | Peptide amphiphiles -- Formation. | |
Title | Multifunctional hybrid networks based on self assembling peptide sequences | en_US |
Type | Thesis | en_US |