Physiologically-Relevant Modes of Membrane Interactions by the Human Antimicrobial Peptide, LL-37, Revealed by SFG Experiments

Antimicrobial peptides (AMPs) could become the next generation antibiotic compounds which can overcome bacterial resistance by disrupting cell membranes and it is essential to determine the factors underlying its mechanism of action. Although high-resolution NMR and other biological studies have pro...

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Bibliographic Details
Published in:Scientific reports 2013-05, Vol.3 (1), p.1854-1854, Article 1854
Main Authors: Ding, Bei, Soblosky, Lauren, Nguyen, Khoi, Geng, Junqing, Yu, Xinglong, Ramamoorthy, Ayyalusamy, Chen, Zhan
Format: Article
Language:English
Subjects:
631/57/2270
631/57/2271
639/638/440
639/638/542
Antimicrobial Cationic Peptides - chemistry
Antimicrobial peptides
Cathelicidins - chemistry
Cell membranes
Cholesterol
Humanities and Social Sciences
Humans
Lipid bilayers
Lipid Bilayers - chemistry
Lipids
Membrane composition
Membranes
multidisciplinary
NMR
Nuclear magnetic resonance
Nuclear Magnetic Resonance, Biomolecular
Peptides
Science
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Summary:Antimicrobial peptides (AMPs) could become the next generation antibiotic compounds which can overcome bacterial resistance by disrupting cell membranes and it is essential to determine the factors underlying its mechanism of action. Although high-resolution NMR and other biological studies have provided valuable insights, it has been a major challenge to follow the AMP-membrane interactions at physiologically-relevant low peptide concentrations. In this study, we demonstrate a novel approach to overcome this major limitation by performing Sum Frequency Generation (SFG) vibrational spectroscopic experiments on lipid bilayers containing an AMP, LL-37. Our results demonstrate the power of SFG to study non-linear helical peptides and also infer that lipid-peptide interaction and the peptide orientation depend on the lipid membrane composition. The observed SFG signal changes capture the aggregating process of LL-37 on membrane. In addition, our SFG results on cholesterol-containing lipid bilayers indicate the inhibition effect of cholesterol on peptide-induced membrane permeation process.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep01854