Cholesterol-Phospholipid Interactions in Membranes

有了这个奖项，化学结构，动力学和机制计划是支持教授保罗阿尔梅达在北卡罗来纳州威尔明顿（UNCW）的大学的基础研究，以解决从脂质双层相互作用的物理化学的角度来看生物膜的组织。阿尔梅达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。阿尔梅达教授将进一步整合该项目的研究和教育组成部分，旨在提高本科生在STEM领域的定量技能，特别是化学，同时促进生物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是一个主要的本科院校，本科生参与研究是一个高度优先事项。什么是独特的本科教育这个项目是，它结合了生物物理化学的积极研究的基本问题与定量方法的广泛使用。由鞘磷脂、不饱和磷脂和胆固醇组成的脂质双层是真核细胞质膜外叶脂质成分的最简单模型。胆固醇与其他脂质的相互作用特别重要，但对它们的了解仍然很少。饱和磷脂和胆固醇的膜已被描述为液体有序相和液体无序相的混合物。然而，在二元混合物中没有观察到相分离。 或者，有序的磷脂和胆固醇已经被提出形成“缩合复合物”。“然后，液体有序相将由这些复合物组成。本研究旨在探索一种替代方案，其中液体有序相是磷脂的热力学状态，其在胆固醇存在下很好地填充，但在其不存在下很少见。该项目旨在通过计算机模拟和实验研究来测试这些相互竞争的假设，并确定越来越多地模仿生物膜组成的脂质混合物中相互作用的大小。

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.