NMR and lateral diffusion in membranes

横向扩散是指蛋白质、脂质和其他分子在活细胞内部和周围的生物膜平面内的随机运动。许多细胞生理过程是由侧扩散控制的。目前测量横向扩散的方法繁琐、耗时，而且可能会造成干扰。在本提案中，我们提出了一种新的技术，用于使用核磁共振（NMR）光谱快速测量膜中的横向扩散，这是一种非干扰技术。这些都是改编自已建立的核磁共振扩散方法，但重新设计，以适应膜的独特困难。此外，我们描述了一个新的模型膜系统，特别为研究横向扩散通过核磁共振。这些新的核磁共振横向扩散方法和新的模型膜系统将用于测量重要的寻膜氟化药物的横向扩散，以及类胡萝卜素，一类具有独特有用光学性质的膜结合分子。此外，横向扩散将在基因治疗应用类型的寡核苷酸诱导的结构域内测量，以及在脂筏内测量，脂筏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/动力学的角度来看，尚不清楚。

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.