Filipin and its interaction with cholesterol in aqueous media studied using static and dynamic light scattering

Aggregation of filipin in aqueous medium and filipin-induced changes in cholesterol micelles have been studied using intensity and dynamic light scattering. The dependencies of filipin aggregate dimensions on concentration, 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 ≈ 110 nm and R_h ≈ 63 nm, referring to the radius of gyration and hydrodynamic radius, respectively. In the concentration range studied (1 μM < C < 30 μM), a low molecular weight species (monomer/dimer) is always present together with the aggregates. In ethanol/ water mixtures, large (R_g ≈ 500 nm), narrow distribution aggregates are formed in the water volume fraction range 0.45 < Φ_H2_O < 0.65. Aggregation also occurs on changing the temperature; In the range 7–37°C, smaller aggregates (10–30 nm) form and the process is only partially 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 filipin interactions with cholesterol, which has been considered a key event in the filipin biochemical mode of action. A reevaluatiori Of this question is suggested and some alternatives are advanced. © 1994 John Wiley & Sons, Inc.