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dc.contributor.advisorGrover, Martha A.
dc.contributor.advisorLynn, David G.
dc.contributor.advisorChampion, Julie A.
dc.contributor.advisorLudovice, Peter J.
dc.contributor.advisorHud, Nicholas V.
dc.contributor.authorHsieh, Ming-Chien
dc.date.accessioned2017-08-17T19:00:35Z
dc.date.available2017-08-17T19:00:35Z
dc.date.created2017-08
dc.date.issued2017-07-17
dc.date.submittedAugust 2017
dc.identifier.urihttp://hdl.handle.net/1853/58708
dc.description.abstractThe peptide assembly mechanism is important for the development of both functional biomaterials and clinical therapies. Although the assembly structures and assembling pathways have been studied for decades, the complex multistep mechanism remains to be clarified. The main goal of this thesis is to investigate the assembly mechanism of functional peptide assemblies. First, the crucial building blocks capable of assembly are synthesized and selected via the dynamic combinatorial networks (DCNs), which yield sequence-defined oligomers with high fidelity. Both experimental analyses and mathematical modeling are applied to confirm the interplay between the chemical distribution and emergent physical transitions in the networks; model discrimination shows that the chemical nature of the DCNs is affected and shifted at different physical stages. Next, to simulate the two-step nucleation process observed in the DCNs, a peptide assembly model is developed with two-step nucleation. The model simulates the phase transitions between different physical phases, and the potential of this model is tested with experimental results from the peptide, Ac-KLVFFAE-NH2. The model is then extended for a polydisperse system, where the peptides undergo oligomerization, to simulate the chemical and physical transitions in the DCNs. The polydisperse model shows that the physical and chemical distribution may reach the steady state independently. The assembly pathway with two-step nucleation is further experimentally investigated with the pH sensitive Abeta(16-22) peptide, which assembles into fiber at neutral pH but tubes at acidic pH. The difference between the nucleation and propagation environments for the two-step nucleation mechanism affects the assembly kinetics and morphological selection. Although Abeta(16-22) assembles into ribbons pH-independently, the ribbon intermediates undergo pH-dependent reaction pathway and transition into different morphologies under different pH conditions. Finally, the catalytic peptide assemblies are analyzed. The methodol substrate is cleaved by Ac-KLVFFAL-NH2 and Ac-OrnLVFFAL-NH2 nanotubes enantioselectively. The experimental results are analyzed with a modified Michaelis-Menten mechanism to resolve the nature of this catalytic system, including the number of peptides per binding site, the enantioselectivity, and the stability of the tubes. The simulations suggest similar binding pocket size for both nanotubes, and the assemblies are stable throughout the entire reaction time. The enantioselectivity for the R- and S-methodol substrate may come from the chemical selectivity of the peptide nanotubes, but not from the difference of the binding affinity, based on the analysis. The results from this thesis provide a comprehensive investigation of the construction of functional peptide assemblies. The building block synthesis and selection, the assembly structure and mechanism, and the functional properties of the peptide assemblies are reported and discussed, which may provide a broad insight about development of peptide-based materials.
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technology
dc.subjectPeptide assembly
dc.subjectKinetics
dc.subjectCatalysis
dc.subjectSystem chemistry
dc.titleKinetic and structural evolution of functional peptide assembling networks
dc.typeDissertation
dc.description.degreePh.D.
dc.contributor.departmentChemical and Biomolecular Engineering
thesis.degree.levelDoctoral
dc.date.updated2017-08-17T19:00:35Z


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