Nearest-Neighbor Recognition in Lipid Bilayers

描述（由申请人提供）：项目总结：“最近邻识别”（NNR）方法是一种有前途的化学技术，可为流体磷脂膜的横向组织提供基本见解。本质上，NNR测量通过检测和量化脂质成为最近邻的趋势来获取膜组织的分子水平快照。本研究的具体目的是使用NNR方法研究天然和非天然膜干扰剂存在下的脂质-肽相互作用、脂质-蛋白相互作用和脂质-脂质相互作用。更具体地说，脂质肽实验将是长期努力的一部分，旨在澄清“规则”管理的流体双层脂质的外周和整体蛋白质的排序。脂质蛋白质的研究，结合transbilayer磷脂相互作用，将提供深入了解一个备受争议的问题，有一个直接关系到细胞膜的结构和功能的一个问题，几乎没有实验数据，即“通信”之间的内部和外部小叶的脂质双层。最后，选定的全身麻醉药和淀粉样β-肽对脂质-脂质相互作用的影响将为两个具有重大生物医学意义的问题提供基本的见解，即全身麻醉药的作用机制和阿尔茨海默病的分子基础。该计划的长期目标是发展对流体双层的二维组织的基本理解，这将有助于使生物膜中的可利用目标更加突出。这种见解将有助于合理设计新型治疗药物。 相关性：细胞膜是细胞的“皮肤”，对维持生命状态至关重要。了解这些膜在分子水平上是如何在两个维度上组织的，应该有助于设计新的和改进的药物;例如，治疗阿尔茨海默病的药物，防止酗酒的药物，以及可用作改进的全身麻醉剂的药物。该计划旨在使用简单的模型系统获得这样的理解。

DESCRIPTION (provided by applicant): PROJECT SUMMARY: The "nearest-neighbor recognition" (NNR) method is a promising chemical technique that provides fundamental insight into the lateral organization of fluid phospholipid membranes. In essence, NNR measurements take molecular-level snapshots of membrane organization by detecting and quantifying the tendency of lipids to become nearest-neighbors. The specific aims of this research are to use the NNR method to investigate lipid-peptide interactions, lipid-protein interactions, and lipid-lipid interactions in the presence of natural and unnatural membrane-perturbing agents. More specifically, lipid-peptide experiments will be part of a long-term effort aimed at clarifying the "rules" governing the sorting of peripheral and integral proteins by lipids in fluid bilayers. Lipid-protein studies, in combination with transbilayer phospholipid interactions, will provide insight into a much-debated issue that has a direct bearing on the structure and function of cell membranes-an issue for which there is virtually no experimental data; that is, the "communication" between the inner and outer leaflets of lipid bilayers. Finally, the effects of selected general anesthetics and amyloid beta-peptides on lipid-lipid interactions will provide fundamental insight into two problems that have major biomedical importance; that is, the mechanism by which general anesthetics function, and the molecular basis of Alzheimer's disease. The long-term objective of this program is to develop a fundamental understanding of the two-dimensional organization of fluid bilayers, which will help bring exploitable targets in biological membranes into sharper focus. Such insight will assist the rational design of novel classes of therapeutic agents. RELEVANCE: Cell membranes are "the skin" of cells, which are essential for maintaining the living state. Understanding how these membranes are organized in two dimensions, at the molecular level, should aid in the design of new and improved drugs; e.g., drugs that can be used to cure Alzheimer's disease, drugs to combat alcohol abuse, and drugs that can be used as improved general anesthetics. This program is aimed at obtaining such an understanding using simple model systems.