Cooperative partition model of nystatin interaction with phospholipid vesicles

被引:57
作者
Coutinho, A
Prieto, M
机构
[1] Univ Tecn Lisboa, Ctr Quim Fis Mol, Inst Super Tecn, P-1049001 Lisbon, Portugal
[2] FCUL, Dept Quim & Bioquim, P-1749016 Lisbon, Portugal
关键词
D O I
10.1016/S0006-3495(03)70032-0
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Nystatin is a membrane-active polyene antibiotic that is thought to kill fungal cells by forming ion-permeable channels. In this report we have investigated nystatin interaction with phosphaticlylcholine liposomes of different sizes (large and small unilamellar vesicles) by time-resolved fluorescence measurements. Our data show that the fluorescence emission decay kinetics of the antibiotic interacting with gel-phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine vesicles is controlled by the mean number of membrane-bound antibiotic molecules per liposome, (A). The transition from a monomeric to an oligomeric state of the antibiotic, which is associated with a sharp increase in nystatin mean fluorescence lifetime from similar to7-10 to 35 ns, begins to occur at a critical concentration of 10 nystatin molecules per lipid vesicle. To gain further information about the transverse location (degree of penetration) of the membrane-bound antibiotic molecules, the spin-labeled fatty acids (5- and 16-doxyl stearic acids) were used in depth-dependent fluorescence quenching experiments. The results obtained show that monomeric nystatin is anchored at the phospholipid/water interface and suggest that nystatin oligomerization is accompanied by its insertion into the membrane. Globally, the experimental data was quantitatively described by a cooperative partition model which assumes that monomeric nystatin molecules partition into the lipid bilayer surface and reversibly assemble into aggregates of 6 +/- 2 antibiotic molecules.
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页码:3061 / 3078
页数:18
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