Small-angle neutron scattering studies of the effects of amphotericin B on phospholipid and phospholipid-sterol membrane structure
Small-angle neutron scattering studies of the effects of amphotericin B on phospholipid and phospholipid-sterol membrane structure
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DOI：
10.1016/j.bbamem.2011.02.012
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发表时间：
2011-06-01
影响因子：
3.4
通讯作者：
Barlow, D. J.
中科院分区：
文献类型：
--
作者：
Foglia, F.;Drake, A. F.;Barlow, D. J.
小角中子散射（SANS）研究已经进行了研究的结构变化诱导的囊泡膜制备（薄膜蒸发）从磷脂和混合磷脂-甾醇混合物，在不同浓度和不同的聚集状态的抗真菌药物，阿朴霉素B（AmB）的存在下。在报道的大多数实验中，制备脂质囊泡，其中将药物直接添加到溶解在有利于AmB单体或聚集体的溶剂中的脂质分散体中，然后将囊泡超声处理至平均尺寸类似于100 nm。然而，也进行了实验，其中药物的胶束分散体被添加到预先形成的脂质和脂质固醇囊泡中。使用磷脂棕榈酰油酰磷脂酰胆碱（POPC）或该脂质与30 mol%胆固醇或30 mol%麦角固醇的混合物制备囊泡。SANS数据的分析表明，无论AmB浓度或聚集状态如何，在所有情况下，纯POPC和混合POPC-甾醇囊泡的膜厚度都增加，总计接近4埃。因此，由药物插入到模型真菌细胞膜中诱导的结构变化（如由POPC-麦角固醇囊泡模拟的）与由其插入到模型哺乳动物细胞膜中引起的结构变化（如由POPC-胆固醇囊泡模拟的）相同。它的结论是，真菌与人类细胞的特异性AmB不会出现，因为（静态）的脂质胆固醇-AmB和脂质麦角固醇-AmB膜之间的结构差异，但更可能的结果，从他们的跨膜孔形成的动力学差异和/或因为两种类型的甾醇-AmB复合物之间的代谢差异。(C)2011 Elsevier B. V.保留所有权利。
Small-angle neutron scattering (SANS) studies have been performed to study the structural changes induced in the membranes of vesicles prepared (by thin film evaporation) from phospholipid and mixed phospholipid-sterol mixtures, in the presence of different concentrations and different aggregation states of the anti-fungal drug, amphotericin B (AmB). In the majority of the experiments reported, the lipid vesicles were prepared with the drug added directly to the lipid dispersions dissolved in solvents favouring either AmB monomers or aggregates, and the vesicles then sonicated to a mean size of similar to 100 nm. Experiments were also performed, however, in which micellar dispersions of the drug were added to pre-formed lipid and lipid-sterol vesicles. The vesicles were prepared using the phospholipid palmitoyloleoylphosphatidylcholine (POPC), or mixtures of this lipid with either 30 mol% cholesterol or 30 mol% ergosterol. Analyses of the SANS data show that irrespective of the AmB concentration or aggregation state, there is an increase in the membrane thickness of both the pure POPC and the mixed POPC-sterol vesicles in all cases amounting to similar to 4 angstrom. The structural changes induced by the drug's insertion into the model fungal cell membranes (as mimicked by POPC-ergosterol vesicles) are thus the same as those resulting from its insertion into the model mammalian cell membranes (as mimicked by POPC-cholesterol vesicles). It is concluded that the specificity of AmB for fungal versus human cells does not arise because of (static) structural differences between lipid-cholesterol-AmB and lipid-ergosterol-AmB membranes, but more likely results from differences in the kinetics of their transmembrane pore formation and/or because of enthalpic differences between the two types of sterol-AmB complexes. (C) 2011 Elsevier B.V. All rights reserved.