Association of polyene antibiotics with sterol-free lipid membranes: I. Hydrophobic binding of filipin to dimyristoylphosphatidylcholine bilayers.
The interaction of filipin III with multilamellar vesicles (MLV) of dimyristoylphosphatidylcholine (DMPC ) was studied by four complementary methods leading to the following results: (1) The modifications of the filipin dichroic spectrum, by adding preformed fluid DMPC MLV, provide evidence of a saturable association with the stoichiometry DMPC/filipin = 4.2 +/- 0.5, constant between 24 and 35 degrees Celsius. (2) Thermograms obtained by differential scanning calorimetry (DSC) on mixtures where filipin is incorporated during the formation of MLV exhibit a high-temperature tail the more marked the higher the filipin content and some structures at temperatures which depend on this content. The corresponding evolution with the temperature of the CD spectra reveals that the characteristic bound filipin spectrum appears at the temperature at which a structure emerges. (3) Titration calorimetry measurements reveal that the association process is exothermic in the temperature range of the DSC endotherms in agreement with the filipin-induced ordering of the lipid chains, previously established by 2H-NMR in the same temperature range (Milhaud et al.(1989) Eur. Biophys. J. 17, 151-158). A discussion of the relevancy of this exothermicity to the hydrophobic effect is developed by referring to the paper by Wimley and White ((1993) Biochemistry 32, 6307-6312).
Milhaud
J
J
Laboratoire de Physicochimie Biomoleculaire et Cellulaire, Universite Paris, Paris, France.
Lancelin
J M
JM
Michels
B
B
Blume
A
A
D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D005372:Filipin / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D015394:Molecular Structure; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D013816:Thermodynamics
D008051:Lipid Bilayers; D008081:Liposomes; D005372:Filipin; D004134:Dimyristoylphosphatidylcholine