DESTABILIZATION OF PHOSPHATIDYLETHANOLAMINE LIPOSOMES AT THE HEXAGONAL PHASE-TRANSITION TEMPERATURE

DESTABILIZATION OF PHOSPHATIDYLETHANOLAMINE LIPOSOMES AT THE HEXAGONAL PHASE-TRANSITION TEMPERATURE
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DOI:
10.1021/bi00350a001
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发表时间:
1986-01-28
期刊:
影响因子:
2.9
通讯作者:
SZOKA, FC
SZOKA, FC
中科院分区:
生物学3区
文献类型:
--
作者:
ELLENS, H;BENTZ, J;SZOKA, FC

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摘要:我们研究了层状-六方相转变温度TH与H+和Ca 2+诱导的磷脂酰乙醇胺(PE)脂质体失稳的初始动力学之间是否伊萨关系。脂质体由二油酰磷脂酰乙醇胺、卵磷脂酰乙醇胺(EPE)或卵磷脂酰胆碱酯交换法制备的磷脂酰乙醇胺(TPE)组成。这些脂质具有良好间隔的层状-六方相转变温度(~ 12、~ 45和~ 57 C),其温度范围允许我们测量双层去稳定化的初始动力学,包括低于和高于。在pH 9.5下制备脂质体。通过使用差示扫描量热法测量EPE和TPE的TH,并且发现TH在低pH或在20 mM Ca 2+存在下在高pH下基本相同。在远低于TH的温度下,在pH 4.5或在pH 9.5的Ca 2+存在下,脂质体聚集、泄漏并经历脂质混合和内容物混合。我们表明,脂质体/脂质体接触参与PE脂质体的不稳定。泄漏、脂质混合和内容物混合的温度依赖性表明,当温度接近特定PE的温度时,泄漏速率大幅提高,并且脂质混合似乎得到增强。然而,在高于TH的温度下,熔融(含水内容物的混合)减少或甚至消失。在和以上,脂质体不稳定的新机制出现,显然取决于PE分子在这些温度下适应新的形态结构的能力。我们认为,这种不稳定demarkes的第一步的途径,最终形成的Hn相。因此,多态性接近PE是一个强大的代理膜不稳定,但需要额外的因素融合。
Revised Manuscript Received August 12, 1985 abstract: We have examined whether there isa relationship between the lamellar-hexagonal phase transition temperature, TH, and the initial kinetics of H+-and Ca2+-induced destabilization of phosphatidylethanolamine (PE) liposomes. The liposomes were composed of dioleoylphosphatidylethanolamine, egg phosphatidylethanolamine (EPE), or phosphatidylethanolamine prepared from egg phosphatidylcholine bytransesterification (TPE). These lipids have well-spaced lamellar-hexagonal phase transition temperatures (~ 12,~ 45, and~ 57 C) in a temperature range that allows us to measure the initial kinetics of bilayer de-stabilization, both belowand above. The liposomes were prepared at pH 9.5. The TH of EPE and TPE was measured by using differential scanning calorimetry, and it was found that the TH was essentially the same at low pH or at high pH in the presence of 20 mM Ca2+. At temperatures well below TH, either at pH 4.5 or at pH 9.5 in the presence of Ca2+, the liposomes aggregate, leak, and undergo lipid mixing and mixing of contents. We show that liposome/liposome contact is involved in the destabilization of the PE liposomes. The temperature dependence of leakage, lipid mixing, and mixing of contents shows that there is a massive enhancement in the rate of leakage when the temperature approaches the of the particular PE and that lipid mixing appears to be enhanced. However, the fusion (mixing of aqueous contents) is diminished or even abolished at temperatures above TH. At and above the, a new mechanism of liposome destabilization arises, evidently dependent upon the ability of the PE molecules to adapt new morphological structures at these temperatures. We propose that this destabilizationdemarks the first step in the pathway to the eventual formation of the Hn phase. Thus, the polymorphism accessible to PE is a powerful agent for membrane destabilization, but additional factors are required for fusion.