Interactions of antimicrobial peptides (AMPs) with model membranes at different pH values

Sandhu, Gagandeep K. (2019) Interactions of antimicrobial peptides (AMPs) with model membranes at different pH values. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Antimicrobial peptides (AMPs) are important components of the innate immune systems of many different organisms. Their amphipathic and cationic characteristics promote interactions with the cell membrane. Gad peptides are rich in histidine, and thus have the potential to exhibit pH-dependent activity. The major focus of this study was to understand how Gad peptides interact with model lipid membranes and how these interactions depend on the peptides’ overall charge and the composition of the model membranes. ²H NMR spectroscopy was used to study the effect of Gad peptides on lipid acyl chain order of model lipid bilayers at different pH values. ²H NMR results revealed that membrane disruption by Gad peptides was not pH-dependent. Zeta potential measurements were used to study the binding of Gad peptides to model lipid membranes. The binding studies showed that for both Gad-1 and Gad-2 at low pH, less peptide binds to the membrane and the peptide interacts with a larger number of lipid molecules. Experiments performed with model membranes containing cardiolipin (CL) in the presence of Gad-1 showed that the presence of CL allows the membrane to accommodate more Gad-1. In the presence of CL the peptide binds more strongly with the membrane and interacts with a larger number of lipids. Taken together, these results suggest that Gad peptides might disrupt membrane integrity by clustering anionic lipids. Clustering of anionic lipids away from zwitterionic lipids by cationic AMPs might be a contributing mechanism, which does not exclude other mechanisms, including the carpet mechanism and pore formation. The chemical shift values of ¹⁵N NMR spectroscopy can give an insight about the positioning of peptides in lipid bilayer surfaces. ¹⁵N NMR observations showed that Gad-1 aligned parallel to the membrane surface. The study of AMP-membrane interactions will help to identify criteria to recognize the important features of natural AMP sequences involved in the antimicrobial action and thus assist in the design of AMP-based antibiotics to help overcome the problem of antimicrobial resistance.

Item Type: Thesis (Doctoral (PhD))
Item ID: 13731
Additional Information: Includes bibliographical references (pages 246-270).
Keywords: Antimicrobial peptides, membrane interactions, pH values
Department(s): Science, Faculty of > Physics and Physical Oceanography
Date: 18 January 2019
Date Type: Submission
Library of Congress Subject Heading: Peptide antibiotics; Bilayer lipid membranes

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