The Water and Nonelectrolyte Permeability Induced in Thin Lipid Membranes by the Polyene Antibiotics Nystatin and Amphotericin B

Nystatin and amphotericin B increase the permeability of thin (<100 A) lipid membranes to ions, water, and nonelectrolytes. Water and nonelectrolyte permeability increase linearly with membrane conductance (i.e., ion permeability). In the unmodified membrane, the osmotic permeability coefficient, P_f, is equal to the tagged water permeability coefficient, (P_d)_w; in the nystatin- or amphotericin B-treated membrane, P_f/(P_d)_w ≈ 3. The unmodified membrane is virtually impermeable to small hydrophilic solutes, such as urea, ethylene glycol, and glycerol; the nystatin- or amphotericin B-treated membrane displays a graded permeability to these solutes on the basis of size. This graded permeability is manifest both in the tracer permeabilities, P_d, and in the reflection coefficients, σ (Table I). The "cutoff" in permeability occurs with molecules about the size of glucose (Stokes-Einstein radius ≊ 4 A). We conclude that nystatin and amphotericin B create aqueous pores in thin lipid membranes; the effective radius of these pores is approximately 4 A. There is a marked similarity between the permeability of a nystatin- or amphotericin B-treated membrane to water and small hydrophilic solutes and the permeability of the human red cell membrane to these same molecules.