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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sterol structure determines the separation of phases and the curvature of the liquid-ordered phase in model membranes
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Sterol structure determines the separation of phases and the curvature of the liquid-ordered phase in model membranes

机译:甾醇结构决定了相膜的分离和模型膜中液相序相的曲率

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摘要

The existence of lipid rafts in biological membranes in vivo is still debated. In contrast, the formation of domains in model systems has been well documented. In giant unilamellar vesicles (GUVs) prepared from ternary mixtures of dioleoyl-phosphatidylcholine/ sphingomyelin/cholesterol, a clear separation of liquid-disordered and sphingomyelin-enriched, liquid-ordered phases could be observed. This phase separation can lead to the fission of the liquid-ordered phase from the vesicle. Here we show that in cholesterol-containing GUVs, the phase separation can involve dynamic redistribution of lipids from one phase into another as a result of a cross-linking perturbation. We found that the molecular structure of a sterol used for the preparation of GUVs determines (ⅰ) its ability to induce phase separation and (ⅱ) the curvature (positive or negative) of the formed liquid-ordered phase. As a consequence, the latter can pinch off to the outside or inside of the vesicle. Remarkably, some mixtures of sterols induce liquid-ordered domains exhibiting both positive and negative curvature, which can lead to a new type of budding behavior in GUVs. Our findings could have implications for the role of sterols in various cell-biological processes such as budding of secretory vesicles, endocytosis, or formation of multivesicular bodies.
机译:体内生物膜中脂筏的存在仍存在争议。相比之下,模型系统中域的形成已得到充分证明。在由二油酰基磷脂酰胆碱/鞘磷脂/胆固醇的三元混合物制备的巨大单层囊泡(GUV)中,可以清楚地分离出液体无序和富含鞘磷脂的液体有序相。这种相分离可导致液相排列的相从囊泡裂变。在这里,我们显示在含胆固醇的GUV中,由于交联扰动,相分离可能涉及脂质从一个相到另一个相的动态重新分布。我们发现用于制备GUV的固醇的分子结构决定了(ⅰ)诱导相分离的能力和(ⅱ)形成的液相有序相的曲率(正或负)。结果,后者会夹到囊泡的外部或内部。值得注意的是,某些固醇混合物会诱导呈正曲率和负曲率的液序结构域,这可能导致GUV中出现一种新的出芽行为。我们的发现可能对固醇在各种细胞生物学过程中的作用具有影响,例如分泌性囊泡出芽,胞吞作用或多囊泡体的形成。

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