Organization of antibiotic amphotericin B in model lipid membranes. A mini review.
Amphotericin B (AmB) is a polyene antibiotic frequently applied in the treatment of fungal infections. According to the general understanding, the mode of action of AmB is directly related to the molecular organization of the drug in the lipid environment, in particular to the formation of pore-like molecular aggregates. Electronic absorption and fluorescence techniques were applied to investigate formation of molecular aggregates of AmB in the lipid environment of liposomes and monomolecular layers formed at the argon-water interface. It appears that AmB dimers, stabilized by van der Waals interactions, are present in the membrane environment along with the aggregates formed by a greater number of molecules. Linear dichroism measurements reveal that AmB is distributed between two fractions of molecules, differently oriented with respect to the bilayer. Molecules in one fraction remain parallel to the plane of the membrane and molecules in the other one are perpendicular. Scanning Force Microscopy imaging of the surface topography of the monolayers formed with AmB in the presence of lipids reveals formation of pore-like structures characterized by the external diameter close to 17 A and the internal diameter close to 6 A. All the findings are discussed in terms of importance of the molecular organization of AmB in the pharmacological action, as well as of the toxic side effects of the drug.
Gruszecki
Wiesław I
WI
Department of Biophysics, Institute of Physics, Maria Skłodowska-Curie University, 20-031 Lublin, Poland. wieslaw@tytan.umcs.lublin.pl
Gagoś
Mariusz
M
Hereć
Monika
M
Kernen
Peter
P
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000666:Amphotericin B / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry*; D019281:Dimerization; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D018625:Microscopy, Atomic Force; D008956:Models, Chemical; D013053:Spectrophotometry
D000935:Antifungal Agents; D008081:Liposomes; D008563:Membrane Lipids; D008567:Membranes, Artificial; D015060:1,2-Dipalmitoylphosphatidylcholine; D000666:Amphotericin B