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MECHANISMS FOR FORMATION OF CELL MEMBRANE DOMAINS

细胞膜域的形成机制

基本信息

批准号：
6498786
负责人：
MICHAEL A EDIDIN
金额：
$ 25.17万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-02-01 至 2004-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6498786
关键词：
HeLa cells atomic force microscopy cell line cell membrane diffusion endocytosis exocytosis fibroblasts fluorescence microscopy membrane activity membrane fusion membrane lipids membrane model membrane proteins membrane structure nanotechnology spectrin

项目摘要

DESCRIPTION (Adapted from abstract): The cell surface mediates the flow of information and metabolites between a cell and its environment. The model of cell surface membranes is evolving from one that emphasizes mobility and autonomy of membrane constituent molecules, to another that emphasizes the lateral concentration of membrane proteins and lipids into patches that are often interpreted as showing that these molecules are confined in membrane domains. While a variety of experiments report the existence of membrane domains, the mechanisms of patch formation, and by implication, the mechanisms of domain creation are largely unknown. Specific interactions between molecules are involved in the formation of very small patches of proteins or lipid but the mechanisms that create large membrane domains, 100s of nm in diameter, are unknown. Without understanding these mechanisms one cannot understand the importance or relevance of membrane domains for cell surface membrane function in normal and abnormal cells. The PI has developed a model, a numerical simulation model based on experimental data, for large-scale domain formation in cell plasma membranes. The model assumes no specific interactions between membrane proteins and lipids. Rather, it depends upon the lateral diffusion coefficients of membrane proteins and lipids, upon the occurrence and stability of barriers to lateral mobility, and upon vesicle traffic to and from the surface. The PI finds that both vesicle traffic, and dynamic barriers to lateral mobility are required to create and maintain lateral heterogeneities in membranes consistent with domains 100s of nm in diameter. In the absence of either barriers to lateral mobility or vesicle traffic, lateral diffusion randomizes the distribution of membrane molecules. The model implies that the apparent concentration of proteins and lipids in membrane domains may be a nonspecific consequence of membrane physics and cell metabolism. The PI proposes to test his model using cells in which the barriers to lateral mobility are defective, sph/sph, alpha-spectrin-deficient, erythroleukemia cells, and cells in which vesicle traffic from and to the surface is inhibited.

描述（改编自摘要）：细胞表面介导信息和代谢物的流动细胞和环境之间的联系细胞表面膜模型从强调膜的流动性和自主性组成分子，另一个强调横向将膜蛋白和脂质浓缩成斑块，通常被解释为这些分子被限制在膜结构域虽然各种各样的实验都表明膜结构域，补丁形成的机制，并通过这意味着，域创建的机制在很大程度上是未知的。分子之间的特定相互作用参与了非常小的蛋白质或脂质斑块，产生直径为100 nm的大膜域是未知的。不了解这些机制，就无法理解膜结构域对细胞表面膜重要性或相关性在正常和异常细胞中发挥作用。 PI开发了一个模型，一个基于实验数据，用于细胞等离子体中的大规模畴形成膜。该模型假设膜之间没有特定的相互作用，蛋白质和脂质。相反，它取决于横向扩散膜蛋白和脂质的系数，在发生和稳定性的障碍，横向流动性，并对囊泡交通，从表面上看。PI发现囊泡运输和需要建立和维持横向流动的动态障碍，膜中的横向不均匀性与100 nm的区域一致直径。如果没有横向流动的障碍，囊泡交通，横向扩散随机分布膜分子该模型表明，膜结构域中蛋白质和脂质的结合可能是非特异性的，膜物理和细胞代谢的结果。 PI建议使用细胞来测试他的模型，在这些细胞中，横向迁移率有缺陷、SPH/SPH、α-血影蛋白缺陷红白血病细胞，以及囊泡往返于表面被抑制。