Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. III. Molecular structure of the polyene antibiotic-cholesterol complexes

Abstract

1. 1. Based on the analysis of the complexes of cholesterol and the polyene antibiotics filipin, amphotericin B, nystatin, etruscomycin and pimaricin, which can be built with space-filling models, and from data on the polyene antibiotic-cholesterol interaction, mechanisms of the polyene antibiotic induced permeability changes in membranes are proposed. 2. 2. The amphotericin B-cholesterol complex is visualised as a circular arrangement of 8 amphotericin B molecules interdigitated by 8 cholesterol molecules. The outside of this complex is hydrophobic, the inside is hydrophilic due to the presence of the hydroxyl groups of the amphotericin B molecules. Two such complexes (half pores) will generate a pore which traverses the membrane. The hydrophilic channel of such a pore has a diameter of about 8 Å. 3. 3. The nystatin-cholesterol and etruscomycin-cholesterol complexes also are visualised as pores. However, the pimaricin-cholesterol complex cannot form a conducting pore because the length of the half pores is considerably less than the length of half the thickness of the lipid core. 4. 4. The filipin-cholesterol complex is visualised as an aggregate of 150–250 Å in diameter oriented in the hydrophobic core of the membrane. This aggregate might be composed of two regular arrays of stacked filipin molecules such that the exterior of this aggregate is hydrophobic due to the presence of the double bonds of filipin to which equal amounts of cholesterol are complexed. The presence of this aggregate causes membrane fragmentation.