Effects of temporins on molecular dynamics and membrane permeabilization in lipid vesicles.
Temporins are a novel family of small (10-13 residues) cationic antimicrobial peptides recently isolated from the skin of the European red frog Rana temporaria. Although recently acquired evidence shows that temporins have the potential to kill bacteria by permeabilizing the cytoplasmic membrane, the molecular mechanisms of membrane selectivity and permeabilization are largely unknown. In this study, it was found that temporins cause the release of fluorescent markers entrapped in phosphatidylcholine liposomes in a manner that depends significantly on the size of the solute. Temporins were also shown to lack a detergent-like effect on lipid vesicles, indicating that marker leakage caused by these peptides is not due to total membrane disruption but to perturbation of bilayer organization on a local scale. Binding of temporins to liposomes did lead to a small increase in lipid hydrocarbon chain mobility, as revealed by EPR spectroscopy of nitroxide-labeled fatty acids incorporated in the bilayer. Reference experiments were conducted using the bee venom peptide melittin, whose properties and behavior in natural and model membrane systems are well known. Our findings for temporins are discussed in relation to the models proposed to date to account for the action of antimicrobial peptides on membranes.
Rinaldi
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AC
Cattedra di Chimica Biologica, Dipartimento di Scienze Mediche Internistiche, Università di Cagliari, Monserrato, Italy.
Di Giulio
A
A
Liberi
M
M
Gualtieri
G
G
Oratore
A
A
Bozzi
A
A
Schininà
M E
ME
Simmaco
M
M
D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability; D003911:Dextrans / Q000032:analysis; D004578:Electron Spin Resonance Spectroscopy; D005452:Fluoresceins / Q000032:analysis; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008555:Melitten / Q000737:chemistry / Q000493:pharmacokinetics*; D008956:Models, Chemical; D010316:Particle Size; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000493:pharmacokinetics*
D023181:Antimicrobial Cationic Peptides; D003911:Dextrans; D005452:Fluoresceins; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; D011506:Proteins; C052526:fluorescein-dextran; C104501:temporin; D008555:Melitten