Peptide-Lipid Interaction Sites Affect Vesicles' Responses to Antimicrobial Peptides
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Yu Shi1, Mingwei Wan1, Lei Fu1
1Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
Abstract:
This article presents coarse-grained molecular dynamics simulations of pore-forming antimicrobial peptide melittin and its interactions with vesicles composed of a mixture of zwitterionic and anionic phospholipids. Besides creating holes in the membrane, the adsorption of melittin also induces vesicle budding, which can develop into vesiculation at high peptide concentrations, as well as vesicle invagination, which can eventually result in a corrugated membrane surface. These rich morphology changes are mediated by the curvature of the vesicles and the peptide concentration. Highly curved vesicles favor the recruitment of melittins with a higher density of binding sites. The peptides mainly penetrate into the membrane surface in monomers via hydrophobic interaction. Lowly curved vesicles recruit melittins with a low density of binding sites. Surplus peptides are prone to form oligomers and shallowly adsorb on the surface of membrane via electrostatic interaction. The penetration of monomers induces membrane pore formation and positive membrane curvature, which promote vesicle budding. The adsorption of oligomers induces negative membrane curvature, which promotes vesicle invagination. This work demonstrates that antimicrobial peptides adopt multiple actions to destroy bacterial membranes.
Insights
Antimicrobial peptides like melittin disrupt bacterial membranes by forming pores and inducing shape changes such as budding and invagination. These effects depend on vesicle curvature and peptide concentration, revealing multifaceted membrane destruction mechanisms.
Area of Science:
- Biophysics
- Materials Science
- Biochemistry
Background:
- Antimicrobial peptides (AMPs) are crucial in innate immunity, targeting bacterial membranes.
- Melittin, a well-studied AMP, is known to form pores in lipid bilayers.
- Understanding AMP-membrane interactions is key to developing new antibiotics.
Purpose of the Study:
- To investigate the complex interactions between the antimicrobial peptide melittin and lipid vesicles.
- To elucidate how vesicle curvature and peptide concentration influence membrane morphology changes.
- To reveal the diverse mechanisms by which melittin disrupts biological membranes.
Main Methods:
- Coarse-grained molecular dynamics simulations were employed.
- Simulations focused on melittin's interaction with mixed zwitterionic and anionic phospholipid vesicles.
- Vesicle morphology and peptide aggregation states were analyzed.
Main Results:
- Melittin induces pore formation, vesicle budding, and vesicle invagination.
- Vesicle curvature and peptide concentration dictate the observed morphological changes.
- Monmeric melittin promotes pore formation and budding, while oligomers induce invagination.
- Vesicle curvature influences melittin recruitment and binding site density.
Conclusions:
- Antimicrobial peptides exhibit multiple strategies to compromise bacterial membranes.
- Melittin's membrane disruption is a complex process influenced by lipid composition, vesicle geometry, and peptide concentration.
- This study provides insights into the biophysical mechanisms underlying AMP efficacy.