Cholesterol-Phospholipid Interactions in Membranes

通过这一奖项，化学结构、动力学和机制计划将支持北卡罗来纳大学威尔明顿分校的Paulo Almeida教授的基础研究，从脂质双层中相互作用的物理化学角度解决生物膜的组织问题。阿尔梅达教授将使用计算机模拟、量热法和荧光光谱学相结合的方法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将这个项目的研究和教育部分整合到一个新的项目中，旨在提高STEM领域本科生的量化技能，特别是化学，同时促进生物科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。威斯康星大学主要是一所本科院校，本科生参与研究是一个高度优先的问题。这个项目在本科教育中的独特之处在于，它结合了生物物理化学活跃研究的基本问题和定量方法的广泛使用。本科生将在早期参与他们的学习，强调在实践中学习。由神经鞘蛋白、不饱和磷脂和胆固醇组成的脂双层是真核细胞质膜外叶脂类成分的最简单模型。胆固醇与其他脂类的相互作用尤其重要，但人们对它们的了解仍然很少。饱和磷脂和胆固醇的膜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被提议形成“缩合复合体”。然后，液体有序相将由这些络合物组成。这项研究试图探索一种替代方案，其中液体有序相是磷脂的热力学状态，磷脂在存在胆固醇的情况下很多，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，并确定日益模仿生物膜组成的脂质混合物中相互作用的程度。

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.