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) ≅ 10(8) ohm-cm(2)) 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 ≈10(2) ohm-cm(2); 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(+)).