Lipid topography and lytic peptides: A lipocentric model for pore-forming antimicrobial peptides.

Paterson, David James (2015) Lipid topography and lytic peptides: A lipocentric model for pore-forming antimicrobial peptides. PhD thesis, University of Glasgow.

Abstract

Linear cationic antimicrobial peptides are a diverse family of membrane-active peptides, linked by physiochemical characteristics that induce membrane disruptive effects, including the formation of membrane spanning pores. They offer potential development as novel antimicrobial therapeutics, due to their high potency and evidenced resistance to bacterial drug resistance mechanisms. Complex lipid-peptide interactions are believed to govern their pore formation activity, and their mechanism of selectivity between prokaryotic and eukaryotic cells. Some peptides (e.g. magainin) show a high degree of selectivity for bacterial cells, while some (e.g. melittin) target bacterial and mammalian cells indiscriminately. Within this report, high-throughput microfluidics is used to investigate the pore formation capabilities, of selective and non-selective antimicrobial peptides, within biomimetic vesicles representing both bacterial and mammalian cells. Microfluidics offers precise control over the exposure of lipid membranes to antimicrobial peptides, allowing the pore-formation process to be elucidated in greater detail than conventional techniques. A new model for their mechanism of action is proposed, where lipid topography and lipid-peptide steric interactions exert influence over both pore formation and the selectivity mechanism. The model has potential to inform the rational drug design of future antimicrobial agents, using linear cationic antimicrobial peptides as a template.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Antimicrobial, peptide, GUV, lipid, microfluidic.
• Subjects: Q Science > Q Science (General); Q Science > QC Physics; Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Engineering > Biomedical Engineering
• Supervisor's Name: Cooper, Professor Jon and Tassieri, Dr. Manlio
• Date of Award: 2015
• Depositing User: Mr David Paterson
• Unique ID: glathesis:2015-73045
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 07 Jun 2019 14:28
• Last Modified: 17 Jul 2019 13:12
• URI: https://theses.gla.ac.uk/id/eprint/73045