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NMR and lateral diffusion in membranes

核磁共振和膜的横向扩散

基本信息

批准号：
138679-2006
负责人：
MacDonald, Peter
金额：
$ 3.96万
依托单位：
University of Toronto
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2008
资助国家：
加拿大
起止时间：
2008-01-01 至 2009-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=391569
关键词：
NMR lateral diffusion membranes

项目摘要

Lateral diffusion refers to the random movement of proteins, lipids and other molecules within the plane of the biomembranes found in and surrounding living cells. Many cellular physiological processes are controlled by lateral diffusion. Current methods for measuring lateral diffusion are cumbersome, time-consuming, and potentially perturbing. In this proposal we present novel techniques for rapidly measuring lateral diffusion in membranes using nuclear magnetic resonance (NMR) spectroscopy, a non-perturbing technique. These are adapted from established NMR diffusion methods, but are re-designed to accommodate the unique difficulties of membranes. In addition, we describe a novel model membrane system especially tailored for the study of lateral diffusion via NMR. These new NMR lateral diffusion methods and new model membrane system will be applied in measuring lateral diffusion of important membrane-seeking fluorinated drugs, as well as carotenoids, a class of membrane-bound molecules with uniquely useful optical properties. Additionally, lateral diffusion will be measured within domains induced by oligonucleotides of the type used for gene therapy applications, and within lipid rafts, a recently identified membrane structure of fundamental functional importance but as yet poorly understood from a structural / dynamics standpoint.

横向扩散指的是蛋白质、脂类和其他分子在活细胞及其周围的生物膜平面内的随机运动。许多细胞的生理过程都是由横向扩散控制的。目前测量横向扩散的方法繁琐、耗时，而且可能会产生扰动。在这项建议中，我们提出了一种新的技术，用于使用核磁共振(核磁共振)谱来快速测量膜中的横向扩散，这是一种非扰动技术。这些技术是从现有的核磁共振扩散方法改编而来的，但经过重新设计，以适应膜的独特困难。此外，我们描述了一种专门用于通过核磁共振研究横向扩散的新的模型膜系统。这些新的核磁共振横向扩散方法和新的模型膜系统将被应用于测量重要的膜寻找氟化物以及类胡萝卜素的横向扩散，类胡萝卜素是一类具有独特有用光学性质的膜结合分子。此外，横向扩散将在用于基因治疗的类型的寡核苷酸诱导的区域内测量，以及在脂筏中测量，这是一种最近发现的具有基本功能重要性的膜结构，但从结构/动力学的角度还知之甚少。