title: Imaging the membrane lytic activity of bioactive peptide latarcin 2a.
abstract: Latarcin 2a (ltc2a, GLFGKLIKKFGRKAISYAVKKARGKH-COOH) is a short linear antimicrobial and cytolytic peptide extracted from the venom of the Central Asian spider, Lachesana tarabaevi, with lytic activity against Gram-positive and Gram-negative bacteria, erythrocytes, and yeast at micromolar concentrations. Ltc2a adopts a helix-hinge-helix structure in membrane mimicking environment, whereas its derivative latarcin 2aG11A (ltc2aG11A, GLFGKLIKKFARKAISYAVKKARGKH-COOH), likely adopts a more rigid structure, demonstrates stronger nonspecific interaction with the zwitterionic membrane, and is potentially more toxic against eukaryotic cells. In this work, interactions of these two ltc2a derivatives with supported "raft" lipid bilayer (1,2-dioleoyl-sn-glycero-3-phosphocholin/egg sphingomyelin/cholesterol 40/40/20mol%) were studied by in situ atomic force microscopy in order to investigate the potential anticancer activity of the peptides since some breast and prostate cancer cell lines contain higher levels of cholesterol-rich lipid rafts than non-cancer cells. Both peptides induced reorganization of the raft model membrane by reducing line tension of the liquid ordered phase. Ltc2aG11A induced membrane thinning likely due to membrane interdigitation. Formation of large pores by the peptides in the bilayer was observed. Cholesterol was found to attenuate membrane disruption by the peptides. Finally, leakage assay showed that both peptides have similar membrane permeability toward various model membrane vesicles.
authors.affiliation: Department of Chemistry, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Won
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ruscito
authors.forename: Anatoli
authors.initials: A
authors.lastname: Ianoul
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D018625:Microscopy, Atomic Force; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism; D013111:Spider Venoms / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013112:Spiders
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008081:Liposomes; D013109:Sphingomyelins; D013111:Spider Venoms; C531159:latarcin 2a, Lachesana tarabaevi; D002784:Cholesterol