title: Physiologically-relevant modes of membrane interactions by the human antimicrobial peptide, LL-37, revealed by SFG experiments.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Bei
authors.initials: B
authors.lastname: Ding
authors.forename: Lauren
authors.initials: L
authors.lastname: Soblosky
authors.forename: Khoi
authors.initials: K
authors.lastname: Nguyen
authors.forename: Junqing
authors.initials: J
authors.lastname: Geng
authors.forename: Xinglong
authors.initials: X
authors.lastname: Yu
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
authors.forename: Zhan
authors.initials: Z
authors.lastname: Chen
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D054804:Cathelicidins / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008051:Lipid Bilayers