Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. II. Temperature dependence of the polyene antibiotic-sterol complex formation

1. The effect of filipin, amphotericin B, nystatin, etruscomycin and pimacirin upon the energy content of the gel → liquid-crystalline phase transition and upon the temperature dependence of the ATPase activity was studied in cholesterol-containing membranes of Acholeplasma laidlawii cells grown on elaidic acid. These experiments prove that the polyene antibiotics form complexes with cholesterol in the A. laidlawii cell membrane. 2. The effect of temperature and different fatty acid composition upon the polyene antibiotic-cholesterol interaction in A. laidlawii cells, lecithin liposomes and in an aqueous dispersion of microcystalline dispersed cholesterol was investigated by (a) ultraviolet spectroscopy, (b) binding experiments, (c) freeze-etch electron microscopy, (d) K+ permeability. From the results of these studies it is suggested that filipin interacts first with cholesterol throughout the membrane forming primary filipin-cholesterol complexes. These complexes subsequently rearrange in the membrane to 150–250 Å diameter aggregates which ultimately fragment the cell membrane. The results obtained for amphotericin B, nystatin and etruscomycin indicte that these antibiotics form much smaller complexes with cholesterol. 3. The primaricin-cholesterol complexes formed in the A. laidlawii and liposomal membranes do not affect membrane permeability. A possible explanation of the haemolytic, fungicidic and fungistatic properties of this polyene antibiotic is suggested.