Cholesterol-Phospholipid Interactions in Membranes

膜中的胆固醇-磷脂相互作用

• 批准号: 1464769
• 负责人: Paulo Almeida
• 金额: $ 24万
• 依托单位: University of North Carolina at Wilmington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1464769&HistoricalAwards=false
• 关键词: Cholesterol; Phospholipid; Interactions; Membranes

With this award, the Chemical Structure, Dynamics and Mechanisms program is supporting fundamental research of Professor Paulo Almeida at the University of North Carolina Wilmington (UNCW) to address the organization of biological membranes from the point of view of the physical chemistry of interactions in the lipid bilayer. Professor Almeida will employ a combination of computer simulations, calorimetry, and fluorescence spectroscopy to investigate the nature and the strength of those interactions. Professor Almeida will further integrate the research and educational components of this project within a new program designed to improve the quantitative skills of undergraduate students in the STEM fields, especially chemistry, while fostering the connections between biological and physical sciences, as a means of bridging the communication gap between these disciplines. UNCW is a primarily undergraduate institution, where participation of undergraduate students in research is a high priority. What is distinctive in this project for undergraduate education is that it combines a fundamental problem of active research in biophysical chemistry with extensive use of quantitative methods. Undergraduates will be involved early on in their studies, emphasizing learning by doing.Lipid bilayers composed of sphingomyelin, unsaturated phospholipids, and cholesterol are the simplest model for the lipid component of the outer leaflet of eukaryotic plasma membranes. The interactions of cholesterol with the other lipids are of particular importance,and they remain poorly understood. Membranes of saturated phospholipids and cholesterol have been described as mixtures of liquid ordered and liquid disordered phases. However, no phase separation has been observed in binary mixtures. Alternatively, ordered phospholipids and cholesterol have been proposed to form a "condensed complex." The liquid ordered phase would then consist of these complexes. This research seeks to explore an alternative in which the liquid ordered phase is a thermodynamic state of the phospholipid, which is well populated in the presence of cholesterol but rare in its absence. The project is designed to test these competing hypotheses through computer simulations and experimental studies, and to determine the magnitudes of the interactions in lipid mixtures that increasingly mimic the composition of biological membranes.

有了这个奖项，化学结构，动力学和机制计划正在支持北卡罗来纳大学威尔明顿大学Paulo Almeida教授的基本研究，以解决从脂质双层中相互作用的物理化学的角度来解决生物膜的组织。 Almeida教授将采用计算机模拟，量热法和荧光光谱的组合来研究这些相互作用的性质和强度。 Almeida教授将进一步将该项目的研究和教育组成部分纳入一个新计划中，旨在提高STEM领域的本科生的定量技能，尤其是化学，同时促进了生物学和物理科学之间的联系，作为弥合这些学科之间沟通差距的一种手段。 UNCW是一家主要的本科机构，本科生参与研究是很高的优先事项。该项目的本科教育项目与众不同的是，它结合了生物物理化学中积极研究的基本问题和广泛使用定量方法。本科生将在他们的研究早期参与其中，强调通过鞘磷脂，不饱和磷脂组成的脂质双层，而胆固醇是真核质子膜外部叶片的脂质成分的最简单模型。胆固醇与其他脂质的相互作用尤其重要，并且它们的理解程度很低。饱和磷脂和胆固醇的膜已被描述为液体有序和液体失调相的混合物。但是，在二元混合物中未观察到相位分离。 另外，已经提出有序的磷脂和胆固醇形成“​​凝结的复合物”。然后，液体排序阶段将由这些复合物组成。这项研究旨在探索一种替代方案，在该替代方案中，液体排序阶段是磷脂的热力学状态，在胆固醇存在下，磷脂的热力学状态良好，但在没有胆固醇的情况下很少。该项目旨在通过计算机模拟和实验研究来检验这些相互竞争的假设，并确定脂质混合物中相互作用的幅度，这些脂质混合物越来越模仿生物膜的组成。