Lipid Asymmetry: A New View on Lipid Dynamics and Membrane Structure

生命过程化学项目支持犹他大学的John C. Conboy教授，他的研究将探索和理解脂质在细胞膜上的运动和脂质组成不对称的建立之间复杂的相互作用。利用PI开发的新应用和频率振动光谱（SFVS）来选择性地探测平面支撑脂质双分子层（PSLB）中的不对称性，将探索平面支撑脂质双分子层中脂质组成不对称与触发器之间的联系。这种新的表面分析方法允许直接检测脂质触发器，而不需要荧光或自旋标记的脂质探针，这可以改变测量的易位率。本研究的目的是利用这种表面分析工具来解决有关跨双层运动和双层系统中脂质不对称建立的一些核心问题。此外，脂质翻转能量学与脂质不对称建立的耦合也将被探讨。这些研究旨在为脂质组成不对称的机制提供物理见解。在美国国家科学基金会化学部生命过程化学项目的支持下，康博伊教授将进行对分子和细胞生物学具有深远影响的研究，并将为解释小分子（如胆固醇）的影响以及跨膜肽对活细胞中脂质翻转和分布的影响提供基础。除了上述的研究将为磷脂跨膜的跨双层运动的研究提供坚实的基础外，研究还可以扩展到脂肪酸、类固醇、激素和其他小分子的交换，这些小分子都显著地调节了脂质膜的物理性质。教育计划的目标是将生物分析化学的概念纳入研究生和本科生的分析课程。在研究生阶段，通过提供PI开发的生物分析化学课程，将继续加强核心分析课程。本课程旨在利用生物科学中使用的最新分析技术，并大量借鉴文献，使学生接触到该领域的最新进展。在本科阶段，将介绍仪器分析实验室的生物分析原理和技术。这不仅会让学生接触到生物分析技术，而且还需要使用基于问题解决的练习。为了培养对生物物理/生物分析化学日益增长的兴趣，一些本科生将参与Conboy教授实验室正在进行的研究。

The Chemistry of Life Processes Program supports Professor John C. Conboy at the University of Utah whose research will explore and understand the complex interplay between the movement of lipid species across the cellular membrane and the establishment of lipid compositional asymmetry. The connection between lipid compositional asymmetry and flip-flop in planar supported lipid bilayers will be explored using a novel application of sum-frequency vibrational spectroscopy (SFVS) developed by the PI to selectively probe the asymmetry in a planar-supported lipid bilayer (PSLB). This new surface analytical method allows for the direct detection of lipid flip-flop without the need for a fluorescent or spin-labeled lipid probe, which can alter the measured translocation rates. The goal of this research is to use this surface analytical tool to address some of the central issues concerning the transbilayer movement and the establishment of lipid asymmetry in bilayer systems. In addition, the coupling of lipid flip-flop energetics to the establishment of lipid asymmetry will also be explored. These studies are aimed at providing physical insight into the mechanism of lipid compositional asymmetry.With the support of the Chemistry of Life Processes Program in the Chemistry Division at the National Science Foundation, Professor Conboy will perform research that has far-reaching implications in molecular and cellular biology and will provide a foundation for interpreting the influence of small molecules such as cholesterol and the influence of transmembrane peptides on lipid flip-flop and distributions in living cells. In addition to the studies outlined above, which will provide a solid foundation for the investigation of transbilayer movement of phospholipids across the membrane, studies could be extended to examine the exchange of fatty acids, steroids, hormones and other small molecules, all of which dramatically modulate the physical properties of lipid membrane. The goal of the education plan is to incorporate the concepts of bioanalytical chemistry into the graduate and undergraduate analytical curriculum. At the graduate level, the continued enhancement of the core analytical curriculum will be achieved by the offering of bioanalytical chemistry, a course that the PI has developed. The course is designed to utilize the most recent analytical techniques used in the biological sciences and draws heavily from the literature, exposing students to the latest advancements in the field. At the undergraduate level, the introduction of bioanalytical principles and techniques in the undergraduate instrumental analysis laboratory will be introduced. This will not only give students exposure to bioanalytical techniques, but will also entail the use of problem-solving based exercises. Several undergraduates will be involved in ongoing research in the laboratory of Professor Conboy, in order to foster a growing interest in biophysical/bioanalytical chemistry.