Visualization of diffusion limited antimicrobial peptide attack on supported lipid membranes

Heath, George R.; Harrison, Patrick L.; Strong, Peter N.; Evans, Stephen D.; Miller, Keith

Abstract

Understanding the mechanism of action of antimicrobial peptides (AMP) is fundamental to the development and design of peptide based antimicrobials. Utilizing fast-scan atomic force microscopy (AFM) we detail the attack of an AMP on both prototypical prokaryotic (DOPC:DOPG) and eukaryotic (DOPC:DOPE) model lipid membranes on the nanoscale and in real time. Previously shown to have a favourable therapeutic index, we study Smp43, an AMP with a helical-hinge-helical topology isolated from the venom of the North African scorpion Scorpio maurus palmatus. We observe the dynamic formation of highly branched defects being supported by 2D diffusion models and further experimental data from liposome leakage assays and quartz crystal microbalance-dissipation (QCM-D) analysis, we propose that Smp43 disrupts these membranes via a common mechanism, which we have termed ‘diffusion limited disruption’ that encompasses elements of both the carpet model and the expanding pore mechanism.

Citation

Heath, G. R., Harrison, P. L., Strong, P. N., Evans, S. D., & Miller, K. (2018). Visualization of diffusion limited antimicrobial peptide attack on supported lipid membranes. Soft matter, 14(29), 6146-6154. https://doi.org/10.1039/c8sm00707a

• Journal Article Type: Article
• Acceptance Date: May 18, 2016
• Online Publication Date: Jul 12, 2018
• Publication Date: 2018
• Deposit Date: May 7, 2019
• Publicly Available Date: May 8, 2019
• Journal: Soft Matter
• Print ISSN: 1744-683X
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 29
• Pages: 6146-6154
• DOI: https://doi.org/10.1039/c8sm00707a
• Keywords: Antimicrobial peptides (AMP); Lipid membranes
• Public URL: https://hull-repository.worktribe.com/output/1738610
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2018/SM/C8SM00707A#!divAbstract
• Additional Information: This is the accepted manuscript of an article published in Soft matter, 2018. The version of record is available at the DOI link in this record.
• Contract Date: May 8, 2019