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Characterisation of cell membrane interaction mechanisms of antimicrobial peptides by electrical bilayer recording

Characterisation of cell membrane interaction mechanisms of antimicrobial peptides by electrical bilayer recording
Characterisation of cell membrane interaction mechanisms of antimicrobial peptides by electrical bilayer recording
Many antimicrobial peptides (AMPs) are cationic host defence peptides (HDPs) that interact with microbial membranes. This ability may lead to implementation of AMPs as therapeutics to overcome the wide-spread antibiotic resistance problem as the affected bacteria may not be able to recover from membrane lysis types of attack. AMP interactions with lipid bilayer membranes are typically explained through three mechanisms, i.e., barrel-stave pore, toroidal pore and carpet models. Electrical bilayer recording is a relatively simple and sensitive technique that is able to capture the nanoscale perturbations caused by the AMPs in the bilayer membranes. Molecular-level understanding of the behaviour of AMPs in relation to lipid bilayers mimicking bacterial and human cell membranes is essential for their development as novel therapeutic agents that are capable of targeted action against disease causing micro-organisms. The effects of four AMPs (aurein 1.2, caerin 1.1, citropin 1.1 and maculatin 1.1 from the skin secretions of Australian tree frogs) and the toxin melittin (found in the venom of honeybees) on two different phospholipid membranes were studied using the electrical bilayer recording technique. Bilayers composed of zwitterionic (DPhPC) and anionic (DPhPC/POPG) lipids were used to mimic the charge of eukaryotic and prokaryotic cell membranes, respectively, so as to determine the corresponding interaction mechanisms for different concentrations of the peptide. Analysis of the dataset corresponding to the four frog AMPs, as well as the resulting dataset corresponding to the bee toxin, confirms the proposed peptide-bilayer interaction models in existing publications and demonstrates the importance of using appropriate bilayer compositions and peptide concentrations for AMP studies.
antimicrobial peptides, bilayer lipid membranes, lipid-peptide interactions, phospholipids, Antimicrobial peptides, Bilayer lipid membranes, Lipid-peptide interactions, Phospholipids
0301-4622
Priyadarshini, Diana
6d23d083-9d75-4ec2-a914-3da18333c388
Ivica, Josip
aacf91f9-3876-4a95-8914-98e94cc524d7
Separovic, Frances
d517a40a-61aa-4f3c-8588-2cd1033eda09
De Planque, Maurits R.R.
a1d33d13-f516-44fb-8d2c-c51d18bc21ba
Priyadarshini, Diana
6d23d083-9d75-4ec2-a914-3da18333c388
Ivica, Josip
aacf91f9-3876-4a95-8914-98e94cc524d7
Separovic, Frances
d517a40a-61aa-4f3c-8588-2cd1033eda09
De Planque, Maurits R.R.
a1d33d13-f516-44fb-8d2c-c51d18bc21ba

Priyadarshini, Diana, Ivica, Josip, Separovic, Frances and De Planque, Maurits R.R. (2022) Characterisation of cell membrane interaction mechanisms of antimicrobial peptides by electrical bilayer recording. Biophysical Chemistry, 281, [106721]. (doi:10.1016/j.bpc.2021.106721).

Record type: Article

Abstract

Many antimicrobial peptides (AMPs) are cationic host defence peptides (HDPs) that interact with microbial membranes. This ability may lead to implementation of AMPs as therapeutics to overcome the wide-spread antibiotic resistance problem as the affected bacteria may not be able to recover from membrane lysis types of attack. AMP interactions with lipid bilayer membranes are typically explained through three mechanisms, i.e., barrel-stave pore, toroidal pore and carpet models. Electrical bilayer recording is a relatively simple and sensitive technique that is able to capture the nanoscale perturbations caused by the AMPs in the bilayer membranes. Molecular-level understanding of the behaviour of AMPs in relation to lipid bilayers mimicking bacterial and human cell membranes is essential for their development as novel therapeutic agents that are capable of targeted action against disease causing micro-organisms. The effects of four AMPs (aurein 1.2, caerin 1.1, citropin 1.1 and maculatin 1.1 from the skin secretions of Australian tree frogs) and the toxin melittin (found in the venom of honeybees) on two different phospholipid membranes were studied using the electrical bilayer recording technique. Bilayers composed of zwitterionic (DPhPC) and anionic (DPhPC/POPG) lipids were used to mimic the charge of eukaryotic and prokaryotic cell membranes, respectively, so as to determine the corresponding interaction mechanisms for different concentrations of the peptide. Analysis of the dataset corresponding to the four frog AMPs, as well as the resulting dataset corresponding to the bee toxin, confirms the proposed peptide-bilayer interaction models in existing publications and demonstrates the importance of using appropriate bilayer compositions and peptide concentrations for AMP studies.

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BIOPHYSCHEM-D-21-00477_R1 - Accepted Manuscript
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Accepted/In Press date: 11 November 2021
e-pub ahead of print date: 16 November 2021
Published date: February 2022
Keywords: antimicrobial peptides, bilayer lipid membranes, lipid-peptide interactions, phospholipids, Antimicrobial peptides, Bilayer lipid membranes, Lipid-peptide interactions, Phospholipids

Identifiers

Local EPrints ID: 455540
URI: http://eprints.soton.ac.uk/id/eprint/455540
ISSN: 0301-4622
PURE UUID: 19249c8b-0635-40a5-807e-aa50be79cf58
ORCID for Maurits R.R. De Planque: ORCID iD orcid.org/0000-0002-8787-0513

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Date deposited: 24 Mar 2022 17:42
Last modified: 17 Mar 2024 06:58

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Contributors

Author: Diana Priyadarshini
Author: Josip Ivica
Author: Frances Separovic
Author: Maurits R.R. De Planque ORCID iD

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