FILIPIN AND ITS INTERACTION WITH CHOLESTEROL IN AQUEOUS-MEDIA STUDIEDUSING STATIC AND DYNAMIC LIGHT-SCATTERING

Aggregation of filipin in aqueous medium and filipin-induced changes i n cholesterol micelles have been studied using intensity and dynamic l ight scattering. The dependencies of filipin aggregate dimensions on c oncentration, solvent, and temperature were studied, and revealed that the aggregates do not have a well-defined geometry, i.e., a critical micelle concentration cannot be detected and stable structures are not formed. The aggregates are of size R(g) approximate to 110 nm and R(h ) approximate to 63 nm, referring to the radius of gyration and hydrod ynamic radius, respectively. In the concentration range studied (1 mu M C < 30 mu M), a low molecular weight species (monomer/dimer) is alwa ys present together with the aggregates. In ethanol/ water mixtures, l arge (R(g) approximate to 500 nm), narrow distribution aggregates are formed in the water volume fraction range 0.45 < Phi(H2O) < 0.65. Aggr egation also occurs on changing the temperature; In the range 7-37 deg rees C, smaller aggregates (10-30 nm) form and the process is only par tially reversible. No pronounced effect of filipin on the structure of the cholesterol micelles was observed (a small increase in R(g) and R (h) is noted). These results rule out any ''specificity'' for the fili pin interactions with cholesterol, which has been considered a key eve nt in the filipin biochemical mode of action. A reevaluation of this q uestion is suggested and some alternatives are advanced. (C) 1994 John Wiley & Sons, Inc.