Cholesterol Rules

Cholesterol Rules
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胆固醇规则

DOI:
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发表时间:
2004
影响因子:
4.8
通讯作者:
L. Bagatolli
L. Bagatolli
中科院分区:
生物学2区
文献类型:
--
作者:
Jorge Bernardino de la Serna;J. Pérez;A. C. Simonsen;L. Bagatolli

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肺表面活性剂是稳定肺部呼吸表面的脂蛋白物质,含有大约等摩尔量的饱和和不饱和磷脂种类以及显着比例的胆固醇。这种脂质组成表明,参与表面活性剂结构的膜可以以面内域的形式异质地组织,源自特定蛋白质和脂质的特定分布。在这里,我们报告了关于由天然肺表面活性剂制成的双层膜的横向组织的新结果,其中通过使用荧光显微镜和原子力显微镜在生理温度下观察到两种不同的微米大小的流体相(流体有序相和流体无序相)的共存。使用荧光标记蛋白 SP-B 和 SP-C 进行的其他实验表明,在生理温度下,这些疏水蛋白仅位于流体无序相中。最有趣的是,在高达 37.5 °C 的温度下,流体相的微观共存得以维持,此时大多数流体有序相都会熔化。这一观察结果表明,这种材料的特定成分自然被设计为处于生理条件下横向结构转变的“边缘”,可能为其机械功能提供特定的结构和动态特性。在天然肺表面活性剂膜中观察到的横向结构受到胆固醇提取的显着影响,而在提取表面活性剂蛋白时未观察到这种影响。此外,天然表面活性剂材料在气液界面的铺展特性也受到胆固醇提取的极大影响,这表明观察到的横向结构与材料的生理相关功能之间存在联系。我们建议可以对表面活性剂的特定脂质成分进行微调,以在生理条件下为表面活性剂蛋白提供结构支架,以在适当的局部密度和脂质成分下发挥作用。
Pulmonary surfactant, the lipid-protein material that stabilizes the respiratory surface of the lungs, contains approximately equimolar amounts of saturated and unsaturated phospholipid species and significant proportions of cholesterol. Such lipid composition suggests that the membranes taking part in the surfactant structures could be organized heterogeneously in the form of inplane domains, originating from particular distributions of specific proteins and lipids. Here we report novel results concerning the lateral organization of bilayer membranes made of native pulmonary surfactant where the coexistence of two distinct micrometer sized fluid phases (fluid ordered and fluid disordered-like phases) is observed at physiological temperatures by using fluorescence microscopy and atomic force microscopy. Additional experiments using fluorescent-labeled proteins SP-B and SP-C show that at physiological temperatures these hydrophobic proteins are located exclusively in the fluid disordered-like phase. Most interestingly, the microscopic coexistence of fluid phases is maintained up to 37.5 °C, where most fluid ordered phases melt. This observation suggests that the particular composition of this material is naturally designed to be at the “edge” of a lateral structure transition under physiological conditions, likely providing particular structural and dynamic properties for its mechanical function. The observed lateral structure in native pulmonary surfactant membranes is dramatically affected by the extraction of cholesterol, an effect not observed upon extraction of the surfactant proteins. Furthermore, the spreading properties of the native surfactant material at the air-liquid interface were also greatly affected by cholesterol extraction, suggesting a connection between the observed lateral structure and a physiologically relevant function of the material. We suggest that the particular lipid composition of surfactant could be finely tuned to provide, under physiological conditions, a structural scaffold for surfactant proteins to act at appropriate local densities and lipid composition.
DOI: 10.1016/s0006-3495(03)75107-8
发表时间: 2003
影响因子: 3.4
作者:
Schief,WilliamR;Antia,Meher;Discher,BohdanaM;Hall,StephenB;Vogel,Viola
通讯作者: Vogel,Viola
DOI: 10.1016/s0006-3495(03)74726-2
发表时间: 2003-11-01
影响因子: 3.4
作者:
Veatch, SL;Keller, SL
通讯作者: Keller, SL
DOI: 10.1073/pnas.96.15.8461
发表时间: 1999-07-20
影响因子: 11.1
作者:
Korlach, J;Schwille, P;Feigenson, GW
通讯作者: Feigenson, GW