Interaction of amphotericin B with cholesterol in monolayers, aqueous solutions, and phospholipid bilayers.
The interaction of amphotericin B (AmB) with cholesterol was investigated in monolayers, aqueous solutions, and phospholipid vesicles. When AmB was mixed with cholesterol, it formed a stable monolayer, implying complex formation in which the stoichiometry was primarily 1:1 AmB:cholesterol. However, the interaction of AmB with cholesterol in aqueous solutions and lipid vesicles was more complex. In aqueous solutions, cholesterol at low concentrations increased the aggregation of AmB. But higher concentrations of cholesterol caused dissociation of the aggregates of AmB due to the formation of AmB-cholesterol complexes. In lipid vesicles, the effect of cholesterol was different from that in aqueous solutions. Both in aqueous solutions and lipid vesicles, the overall dissociation of AmB molecules occurred on interaction with cholesterol. In addition, the interaction of lipid membranes with AmB-cholesterol complexes was investigated by differential scanning calorimetry. The incorporation of AmB into lipid bilayers led to broadening of the lipid transition and a slight decrease in the transition enthalpy, showing that one lipid molecule per AmB molecule was immobilized. However, the number of immobilized lipid molecule per AmB molecule increased in the coexistence of cholesterol, due to the complex formation between AmB and cholesterol.
Saka
Y
Y
Department of Natural Science, Osaka Women's University, 2-1, Daisen-cho, Sakai, Osaka 590, Japan.
Mita
T
T
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000666:Amphotericin B / Q000737:chemistry*; D002151:Calorimetry; D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008567:Membranes, Artificial; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D014867:Water
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D012996:Solutions; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D000666:Amphotericin B; D002784:Cholesterol