Binding of nystatin and amphotericin B with sterol-free L-dilauroylphosphatidylcholine bilayers resulting in the formation of dichroic lipid superstructures.
Interactions of multilamellar vesicles (MLV) of dilauroylphosphatidylcholine (DLPC) with the polyene antibiotics, amphotericin B (AmB) and nystatin (Ny), were followed by circular dichroism (CD). These interactions proceed with both antibiotics through a slow association with high [DLPC]/[antibiotic] stoichiometric molar ratios (> or = 130), at room temperature for which DLPC membranes are in a fluid state. Microscopic investigations of the spatial distributions of the antibiotic and the MLV in the mixtures revealed that MLV form clusters inside which the antibiotic is strongly concentrated and lipid superstructures appear. Concomitantly with the appearance of these superstructures a DLPC dichroic signal emerges. This observation indicates that the chiral properties of antibiotic oligomers can induce a chirality of the DLPC molecules which are bound to them. These results support the hypothesis of a recent molecular modeling of AmB oligomers which postulates that their chiral properties result from a chiral assemblage of antibiotic molecules (Millié et al., J. Phys. Chem. B, in press).
Milhaud
J
J
Laboratoire de Physicochimie Biomoleculaire et cellulaire (ESA 7033), Université Paris VI, France.
Michels
B
B
D000666:Amphotericin B / Q000378:metabolism*; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000378:metabolism*; D009761:Nystatin / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D013054:Spectrophotometry, Atomic
D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D009761:Nystatin; C015153:1,2-dilauroylphosphatidylcholine; D000666:Amphotericin B