Brown P M, Silvius J R
Department of Biochemistry, McGill University, Montréal, Québec, Canada.
Biochim Biophys Acta. 1989 Apr 14;980(2):181-90. doi: 10.1016/0005-2736(89)90398-2.
We have used lipid mixing, contents mixing and contents-leakage assays to characterize the divalent cation-mediated interactions of vesicles composed of various headgroup-modified analogues of phosphatidylethanolamine, PE (N- and C-2-alkylated derivatives, and analogues with increased separations of the phosphoryl and amino groups) together with a low mole percentage of phosphatidylserine (PS). Vesicles containing different structural analogues of PE exhibit marked differences, both in the threshold divalent cation concentrations that are required to initiate vesicle-vesicle interactions and in the rates of contents mixing and leakage observed at suprathresholds divalent cation concentrations. The efficiencies of divalent cation-promoted contents leakage, and to a slightly lesser extent those of contents mixing, for PS/PE (analogue) vesicles show a marked inverse correlation with the lamellar-to-hexagonal II transition temperature (TH) of the PE (analogue) component. However, the destabilization kinetics for such vesicles show no abrupt changes over the temperature range around the equilibrium TH value measured for the vesicle lipids. Vesicles combining PS with different PE analogues exhibit divalent cation thresholds for aggregation that are not correlated with the TH values of the PE (analogue) components but appear instead to be correlated with the equilibrium interbilayer separations measured in multilamellar dispersions of these species. We have identified headgroup-modified analogues of PE that can be used to prepare vesicles that fuse more rapidly under a given set of conditions, or that show a bette ratio of fusion-to-contents-leakage rates, than do PE-containing vesicles. These results may be useful both for understanding better the bases for the high fusion-supporting ability of PE and for the preparation of lipid vesicles 'tailored' for particular practical applications.
我们使用脂质混合、内容物混合和内容物泄漏分析方法，来表征由磷脂酰乙醇胺（PE）的各种头部基团修饰类似物（N-和C-2-烷基化衍生物，以及磷酰基和氨基间距增加的类似物）与低摩尔百分比的磷脂酰丝氨酸（PS）组成的囊泡的二价阳离子介导的相互作用。含有不同结构类似物的PE的囊泡，在引发囊泡-囊泡相互作用所需的阈值二价阳离子浓度，以及在高于阈值的二价阳离子浓度下观察到的内容物混合和泄漏速率方面，都表现出显著差异。对于PS/PE（类似物）囊泡，二价阳离子促进的内容物泄漏效率，以及在稍小程度上的内容物混合效率，与PE（类似物）组分的层状到六方II相转变温度（TH）呈现出显著的负相关。然而，此类囊泡的去稳定动力学在围绕囊泡脂质测量的平衡TH值的温度范围内没有突然变化。将PS与不同PE类似物结合的囊泡表现出的聚集二价阳离子阈值，与PE（类似物）组分的TH值无关，反而似乎与在这些物质的多层分散体中测量的平衡双层间距相关。我们已经鉴定出PE的头部基团修饰类似物，它们可用于制备在给定条件下比含PE的囊泡融合更快，或显示出更好的融合与内容物泄漏速率比的囊泡。这些结果对于更好地理解PE的高融合支持能力的基础，以及制备针对特定实际应用“量身定制”的脂质囊泡可能都有用。
