Cholesterol Precipitation from Real and Model Biomembranes

真实生物膜和模型生物膜中的胆固醇沉淀

• 批准号: 9722818
• 负责人: Gerald Feigenson
• 金额: $ 27万
• 依托单位: Cornell University
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9722818&HistoricalAwards=false
• 关键词: Cholesterol; Precipitation; Real; Model; Biomembranes

9722818 Feigenson A goal of this work is to find the solubility limit of cholesterol in model and real biomembranes, above which cholesterol precipitates from the bilayer as a crystal. This project has four main components: (I) defined mixtures of cholesterol and phospholipids are used as models for biomembranes; (ii) novel methods, together with X-ray diffraction experiments, are developed that are sensitive to the formation of coexisting phases; (iii) Monte Carlo computer simulations are used in order to find the cholesterol and phospholipid interaction energy over the entire range of compositions; (iv) crystalline cholesterol monohydrate formation is probed in cultured mammalian cells. These experiments will enable construction of 3-component phase diagrams that describe the mixing of cholesterol with two different phospholipids. The theoretical part of this project develops a model to describe the microscopic interaction energy between cholesterol and its neighboring lipids. Guided by these model system studies, X-ray diffraction and electron and optical microscopy of cells in culture will determine cholesterol solubility limits in real biomembranes. The overall objective of this project is to define and measure excessive cholesterol content, for a given membrane. These basic studies will clarify mechanisms of cholesterol accumulation within cells and cellular signals for its uptake. ***

9722818 Feigenson这项工作的目标是找到胆固醇在模型和真实生物膜中的溶解度极限，在此极限之上，胆固醇从双层中以晶体形式析出。该项目有四个主要组成部分：(1)确定的胆固醇和磷脂混合物用作生物膜模型；（ii）新方法和x射线衍射实验对共存相的形成很敏感；（三）利用蒙特卡罗计算机模拟，找出整个组合物范围内胆固醇和磷脂的相互作用能；（iv）在培养的哺乳动物细胞中探测结晶胆固醇一水化合物的形成。这些实验将使构建描述胆固醇与两种不同磷脂混合的三组分相图成为可能。该项目的理论部分开发了一个模型来描述胆固醇及其邻近脂质之间的微观相互作用能量。在这些模型系统研究的指导下，培养细胞的x射线衍射、电子和光学显微镜将确定胆固醇在真实生物膜中的溶解度极限。该项目的总体目标是定义和测量给定膜的过量胆固醇含量。这些基础研究将阐明细胞内胆固醇积累的机制和细胞摄取胆固醇的信号。＊＊＊