Siegel D P
Biophys J. 1986 Jun;49(6):1171-83. doi: 10.1016/S0006-3495(86)83745-6.
Results of a kinetic model of thermotropic L alpha----HII phase transitions are used to predict the types and order-of-magnitude rates of interactions between unilamellar vesicles that can occur by intermediates in the L alpha----HII phase transition. These interactions are: outer monolayer lipid exchange between vesicles; vesicle leakage subsequent to aggregation; and (only in systems with ratios of L alpha and HII phase structural dimensions in a certain range or with unusually large bilayer lateral compressibilities) vesicle fusion with retention of contents. It was previously proposed that inverted micellar structures mediate membrane fusion. These inverted micellar structures are thought to form in all systems with such transitions. However, I show that membrane fusion probably occurs via structures that form from these inverted micellar intermediates, and that fusion should occur in only a sub-set of lipid systems that can adopt the HII phase. For single-component phosphatidylethanolamine (PE) systems with thermotropic L alpha----HII transitions, lipid exchange should be observed starting at temperatures several degrees below TH and at all higher temperatures, where TH is the L alpha----HII transition temperature. At temperatures above TH, the HII phase forms between apposed vesicles, and eventually ruptures them (leakage). In most single-component PE systems, fusion via L alpha----HII transition intermediates should not occur. This is the behavior observed by Bentz, Ellens, Lai, Szoka, et al. in PE vesicle systems. Fusion is likely to occur under circumstances in which multilamellar samples of lipid form the so-called "inverted cubic" or "isotropic" phase. This is as observed in the mono-methyl DOPE system (Ellens, H., J. Bentz, and F. C. Szoka. 1986. Fusion of phosphatidylethanolamine containing liposomes and the mechanism of the L alpha-HII phase transition. Biochemistry. In press.) In lipid systems with L alpha----HII transitions driven by cation binding (e.g., Ca2+-cardiolipin), fusion should be more frequent than in thermotropic systems.
热致Lα----HII相变动力学模型的结果被用于预测单室囊泡之间相互作用的类型和数量级速率,这些相互作用可通过Lα----HII相变的中间体发生。这些相互作用包括:囊泡间外层单分子层脂质交换;聚集后囊泡泄漏;以及(仅在Lα和HII相结构尺寸比例处于一定范围内或具有异常大的双层横向压缩性的系统中)囊泡融合且内容物保留。先前有人提出反胶束结构介导膜融合。据认为,这些反胶束结构在所有具有此类转变的系统中都会形成。然而,我表明膜融合可能通过由这些反胶束中间体形成的结构发生,并且融合仅应发生在能够形成HII相的脂质系统的一个子集中。对于具有热致Lα----HII转变的单组分磷脂酰乙醇胺(PE)系统,脂质交换应在比TH低几度的温度下开始观察到,并且在所有更高温度下都能观察到,其中TH是Lα----HII转变温度。在高于TH的温度下,HII相在相邻囊泡之间形成,并最终使它们破裂(泄漏)。在大多数单组分PE系统中,通过Lα----HII转变中间体的融合不应发生。这就是Bentz、Ellens、Lai、Szoka等人在PE囊泡系统中观察到的行为。在脂质形成所谓“反立方”或“各向同性”相的多分子层样品的情况下,融合可能会发生。这正如在单甲基DOPE系统中所观察到的(Ellens,H.,J. Bentz,和F. C. Szoka. 1986. 含磷脂酰乙醇胺脂质体的融合及Lα-HII相变的机制。生物化学。即将发表。)在由阳离子结合(例如Ca2 + -心磷脂)驱动Lα----HII转变的脂质系统中,融合应比在热致系统中更频繁。