Molecular Interaction and Lateral Domain Formation in Monolayers Containing Cholesterol and Phosphatidylcholines with Acyl- or Alkyl-Linked C16 Chains

Molecular Interaction and Lateral Domain Formation in Monolayers Containing Cholesterol and Phosphatidylcholines with Acyl- or Alkyl-Linked C16 Chains
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含有酰基或烷基连接的 C16 链的胆固醇和磷脂酰胆碱的单分子层中的分子相互作用和侧向结构域形成

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发表时间:
1996
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通讯作者:
J. Slotte
J. Slotte
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作者:
P. Mattjus;R. Bittman;J. Slotte

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在混合单层中,用荧光显微镜观察侧区的形成,用胆固醇氧化酶来探测甾醇-磷脂相互作用的相对强度,研究了胆固醇与具有酰基或烷基连接的C16链的磷脂酰胆碱的相互作用。本研究的磷脂酰胆碱包括1,2-二棕榈酰甘油-3-磷胆碱(DPPC)、1-palmitoyl-2-O-hexadecyl-sn-glycero-3-phosphocholine(PHPC)、1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phosphocholine(HPPC)和1,2-O-二十六烷基甘油-3-磷胆碱(DHPC)。当用荧光显微镜(以0.5mol%NBD-胆固醇为探针)观察到凝液相的二维结晶时,DPPC和HPPC在液体膨胀到液凝相转变的起始压力下都表现出相似的液凝相成核和生长(尽管凝聚相的大小和形状不同)。然而,对于PHPC和DHPC,从这些脂类的力-面积等温线确定的相变开始之前,侧向凝聚相就很明显了。因此,根据烷基官能团的位置不同,凝聚相的形成方式也不同。当胆固醇与这些磷脂酰胆碱(摩尔分数分别为20%、25%或33%)混合时,形成富含胆固醇的凝聚区。胆固醇-DPPC和胆固醇-PHPC混合单分子膜的结构域形态相似,而胆固醇-HPPC和胆固醇-DHPC混合单分子膜具有部分不同的结构域形态,富含胆固醇的结构域融合更广泛。当用胆固醇氧化酶探测胆固醇与每种磷脂酰胆碱分子间结合的相对强度时,观察到与DPPC(由胆固醇氧化酶催化的最高胆固醇氧化速率)之间的相互作用最松散,而在PHPC(较低的胆固醇氧化速率)中结合较强,在HPPC和DHPC混合单层中更强(未检测到氧化)。总之,磷脂酰胆碱分子的1位或2位(或两位)的烷基官能团的存在显著改变了其在单层膜中的性质。
The interactions of cholesterol with phosphatidylcholines having acyl- or alkyl-linked C16 chains have been determined in mixed monolayers using fluorescence microscopy to visualize lateral domain formation and cholesterol oxidase to probe for the relative strength of sterol-phospholipid interaction. The phosphatidylcholines of this study included 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1-palmitoyl-2-O-hexadecyl-sn-glycero-3-phosphocholine (PHPC), 1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phosphocholine (HPPC), and 1,2-O-dihexadecyl-sn-glycero-3-phosphocholine (DHPC). As the two-dimensional crystallization of the liquid-condensed phase was visualized with fluorescence microscopy (using 0.5 mol % NBD-cholesterol as a probe), both DPPC and HPPC displayed a similar nucleation and growth of the liquid-condensed phase at the onset pressure of the liquid-expanded to liquid-condensed phase transition (although the size and shapes of the condensed domains differed). However, with both PHPC and DHPC, laterally condensed phases were evident well before the onset of the phase transition as determined fro the force-area isotherms of these lipids. Therefore, the pattern of formation of condensed phases was different, depending on the position of the alkyl function. When cholesterol was mixed with these phosphatidylcholines (at 20, 25, or 33 mol %), cholesterol-rich condensed domains were formed. The domain morphology was similar in cholesterol-DPPC and cholesterol-PHPC mixed monolayers, whereas cholesterol-HPPC and cholesterol-DHPC mixed monolayers had partly different domain morphologies, with more extensive fusion of the cholesterol-rich domains. When cholesterol oxidase was used to probe for the relative strength of intermolecular association between cholesterol and each of the phosphatidylcholines, it was observed that the interaction was loosest with DPPC (highest rate of cholesterol oxidation catalyzed by cholesterol oxidase), whereas the association was somewhat stronger in PHPC (lower rate of cholesterol oxidation) and much stronger in HPPC and DHPC mixed monolayers (no detectable oxidation). In conclusion, the presence of an alkyl function at position 1 or 2 (or both) of a phosphatidylcholine molecule markedly changed its properties in monolayer membranes.