Antimicrobial Peptide-Functionalized Biomaterials: From Synthesis to Membrane Biophysics
AuthorDoole, Fathima T.
DOPC and DOPE lipids
solid-state NMR spectroscopy
AdvisorBrown, Michael F.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
EmbargoRelease after 12/18/2024
AbstractThis research addresses the challenges associated with traditional antimicrobial peptide (AMP) anchoring by introducing an innovative artificial biomaterial platform, thereby enhancing AMP stability and efficacy. In Chapter 1, we establish the importance of studying lipid diversity for comprehending AMP-membrane interactions and underline our objectives: the creation of a smart biopolymer with scaffolds, spacers, and AMPs, and exploring bacterial versus mammalian lipid composition in AMP selectivity through solid-state NMR spectroscopy. Chapter 2 details the methodologies employed, ranging from biomaterial synthesis using the E. coli expression system to characterization techniques like dynamic light scattering and solid-state NMR methods. Chapter 3 introduces our unique biopolymer tether approach for augmenting AMP activity, supported by results from genetic modifications. Chapter 4 delves into the impact of lamellar and nonlamellar lipid compositions on bilayer properties, offering novel methodologies to study unsaturated lipid systems, which were previously challenging. Chapter 5 focuses on the quantitative analysis of the role of cholesterol in lipid bilayer rigidity, permeability, and micro-mechanics, revealing a correlation between bending rigidity and lipid packing. Building on these insights, Chapter 6 examines the effects of the Cathelicidin antimicrobial peptide LL37 and cholesterol on DOPE and DOPC membranes. Combining the probe lipid approach with molecular dynamics simulations, this research offers unprecedented atomic-level insights into the interactions between AMPs, cholesterol, and lipid bilayers. Collectively, the study provides a comprehensive understanding of AMP activity and selectivity in various lipid environments.
Degree ProgramGraduate College