Dynamics in Peptide Folding, Surface Activity and Self-assembly
Item
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Title
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Dynamics in Peptide Folding, Surface Activity and Self-assembly
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Identifier
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d_2009_2013:3a13c4db58b1:11037
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identifier
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11286
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Creator
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Jain, Vikas Parasmal,
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Contributor
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Raymond S. Tu
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Date
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2011
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biomedical engineering | Biomechanics | Molecular biology | Binding kinetics | Dynamic Folding | Peptide design | Self-assembly
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Abstract
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Tunable amphiphilicity is an attractive tool for applications ranging from separation processes to drug delivery. We have designed an alpha-helical peptide containing 23 amino acids, incorporating hydrophobic residues on one side (leucines and alanines) and hydrophilic residues on the opposite side. Our model peptide shows switchable surface activity, where the folded form (alpha-helix) of the peptide is amphiphilic and the unfolded form (random coil) is not amphiphilic. Subsequently, we apply this dynamically folding peptide to examine DNA condensation, starting from a fundamental new understanding of biomolecular surface activity and ending with systems that fold, self-assemble, and condense to states relevant for drug delivery.;We demonstrate four properties to show that our model peptide can be applied in dynamic condensation processes. First, circular dichroism shows that our model peptide has transient secondary structure. We show that we can control the equilibrium structure and, thus, control the surface activity. Second, Pendant bubble tensiometry is used to characterize the dynamic amphiphilicity (surface activity) due to folding of the model peptide. Together, the circular dichroism and pendant bubble tensiometer study shows that our model peptide responds to environmental stimuli with dynamic folding and surface activity. Third, modeling of the dynamic surface activity/amphiphilicity helps in understanding the effect of different factors on folding of the peptide and its transport to the air-water interface. The results indicate that the kinetic adsorption rate of the folded peptide onto air-water interface dominates the dynamic process, which contrasts many head-tail surfactants where diffusion typically dominates over kinetics in the adsorption to interfaces. Additionally, the numerical solution is compared with an asymptotic solution, showing agreement with our findings that the fundamental dynamics of the tunable surface-active peptide are indeed controlled by the adsorption step. Fourth, multi-angle light scattering is used to study the kinetics of DNA condensation. We quantify the rapid self-assembly of the DNA-peptide complex formation, corroborating our hypothesis that the kinetics of DNA condensation are controlled by the folding dynamics of the model peptide. We also compare the scattering data of our model peptide with a common non-folding condensing agent, Spermidine. This work shows our ability to engineer synthetic peptides where tunable amphiphilicity coincides with biomolecular binding, and these rationally designed systems can be used as a potential tool for applications ranging from gene delivery to separations.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Engineering
