INTERACTION OF FILIPIN AND DERIVATIVES WITH ERYTHROCYTE MEMBRANES AND LIPID DISPERSIONS - ELECTRON MICROSCOPIC OBSERVATIONS

The effect of the polyene antibiotic, filipin, on the morphology of erythrocyte membranes and lipid dispersions has been investigated with the electron microscope using negative staining (phosphotungstate). Filipin induces pit formation in rat and human erythrocytes; similar pits are also produced by the antibiotic in lecithin-cholesterol dispersions. Pit formation requires the presence of cholesterol. Evidence is presented which suggests that the light ring surrounding each pit may consist predominately, if not exclusively, of sterol which had interacted with the antibiotic. Pits are not produced in lecithin-cholesterol dispersions by derivatives of the antibiotic which have little (perhydrofilipin) or no (irradiated filipin) hemolytic activity. Thus, the characteristic lamellar pattern of the dispersions is retained in the presence of the irradiated derivative, whereas perhydrofilipid has an effect which is apparently similar to that produced by lyso-lecithin. The pits produced by filipin resemble those produced in human erythrocyte membranes by immune lysis in the presence of complement but are quite different from those produced by saponin. The relevance of these observations to current concepts regarding the mode of filipin action is discussed. It is suggested that filipin may interfere with the ability of cholesterol to stabilize the bilayer configuration of phos-pholipids. Experiments which suggest that the sterol can function as a stabilizer are described.