title: MSI-78, an analogue of the magainin antimicrobial peptides, disrupts lipid bilayer structure via positive curvature strain.
abstract: In this work, we present the first characterization of the cell lysing mechanism of MSI-78, an antimicrobial peptide. MSI-78 is an amphipathic alpha-helical peptide designed by Genaera Corporation as a synthetic analog to peptides from the magainin family. (31)P-NMR of mechanically aligned samples and differential scanning calorimetry (DSC) were used to study peptide-containing lipid bilayers. DSC showed that MSI-78 increased the fluid lamellar to inverted hexagonal phase transition temperature of 1,2-dipalmitoleoyl-phosphatidylethanolamine indicating the peptide induces positive curvature strain in lipid bilayers. (31)P-NMR of lipid bilayers composed of MSI-78 and 1-palmitoyl-2-oleoyl-phosphatidylethanolamine demonstrated that the peptide inhibited the fluid lamellar to inverted hexagonal phase transition of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine, supporting the DSC results, and the peptide did not induce the formation of nonlamellar phases, even at very high peptide concentrations (15 mol %). (31)P-NMR of samples containing 1-palmitoyl-2-oleoyl-phosphatidylcholine and MSI-78 revealed that MSI-78 induces significant changes in the bilayer structure, particularly at high peptide concentrations. At lower concentrations (1-5%), the peptide altered the morphology of the bilayer in a way consistent with the formation of a toroidal pore. Higher concentrations of peptide (10-15%) led to the formation of a mixture of normal hexagonal phase and lamellar phase lipids. This work shows that MSI-78 induces significant changes in lipid bilayers via positive curvature strain and presents a model consistent with both the observed spectral changes and previously published work.
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Hallock
authors.forename: Dong-Kuk
authors.initials: DK
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Ramamoorthy
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D046911:Macromolecular Substances; D008560:Membrane Fluidity; D008968:Molecular Conformation; D009038:Motion; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D016062:Porosity; D011498:Protein Precursors / Q000737:chemistry; D013314:Stress, Mechanical; D029867:Xenopus Proteins
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D046911:Macromolecular Substances; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011498:Protein Precursors; D029867:Xenopus Proteins; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; C056453:promagainin protein, Xenopus; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; C093828:pexiganan