Zwitterionic phospholipids and sterols modulate antimicrobial peptide-induced membrane destabilization
A James Mason1, Arnaud Marquette, Burkhard Bechinger
1Faculté de chimie, Université Louis Pasteur/Centre National de la Recherche Scientifique UMR 7177, Institut le Bel, Strasbourg, France. james.mason@kcl.ac.uk
Biophysical Journal
|September 4, 2007
Summary
Sterols like cholesterol and ergosterol protect cell membranes from antimicrobial peptides. This explains why bacteria are susceptible while fungi and humans are more resistant to these peptides.
Area of Science:
- Membrane biophysics
- Antimicrobial peptide research
- Lipid-protein interactions
Background:
- Cationic antimicrobial peptides (AMPs) target cell membranes, but host cell discrimination is key.
- Membrane composition, particularly sterols, influences AMP efficacy and selectivity.
Purpose of the Study:
- To investigate how membrane sterols (cholesterol, ergosterol) affect the interaction between the antimicrobial peptide pleurocidin and model membranes.
- To elucidate the molecular mechanisms underlying differential membrane sensitivity to AMPs.
Main Methods:
- Utilized intrinsic tryptophan fluorescence and circular dichroism to monitor peptide binding.
- Employed 2H solid-state NMR of deuterated lipids to assess lipid acyl chain disruption.
- Investigated model membranes with varying sterol concentrations and lipid compositions.
Main Results:
- Sterol presence increases lipid acyl chain order in model membranes, with cholesterol and ergosterol showing differential effects.
- Acyl chain ordering is also influenced by the zwitterionic phospholipid headgroup in mixed anionic membranes.
- Sterols protect anionic membranes from the disruptive actions of pleurocidin.
Conclusions:
- Sterols act as a protective barrier, modulating the interaction between AMPs and cell membranes.
- This provides a molecular explanation for the varying susceptibility of bacteria, fungi, and higher organisms to AMPs based on their membrane sterol content.
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