The Interaction of Polyene Antibiotics with Thin Lipid Membranes

Optically black, thin lipid membranes prepared from sheep erythrocyte lipids have a high dc resistance (R_m ≅ 10⁸ ohm-cm²) when the bathing solutions contain NaCl or KCl. The ionic transference numbers (T_i) indicate that these membranes are cation-selective (T_Na ≅ 0.85; T_Cl ≅ 0.15). These electrical properties are independent of the cholesterol content of the lipid solutions from which the membranes are formed. Nystatin, and probably amphotericin B, are cyclic polyene antibiotics containing ≈36 ring atoms and a free amino and carboxyl group. When the lipid solutions used to form membranes contained equimolar amounts of cholesterol and phospholipid, these antibiotics reduced R_m to ≈10² ohm-cm²; concomitantly, T_Cl became ≅0.92. The slope of the line relating log R_m and log antibiotic concentration was ≅4.5. Neither nystatin (2 x 10^-5 M) nor amphotericin B (2 x 10^-7 M) had any effect on membrane stability. The antibiotics had no effect on R_m or membrane permselectivity when the lipids used to form membranes were cholesterol-depleted. Filipin (10^-5 M), an uncharged polyene with 28 ring atoms, produced striking membrane instability, but did not affect R_m or membrane ionic selectivity. These data suggest that amphotericin B or nystatin may interact with membrane-bound sterols to produce multimolecular complexes which greatly enhance the permeability of such membranes for anions (Cl^-, acetate), and, to a lesser degree, cations (Na⁺, K⁺, Li⁺).