NMR and lateral diffusion in membranes

侧向扩散是指蛋白质、脂质和其他分子在活细胞中和活细胞周围的生物膜平面内的随机运动。 许多细胞的生理过程是由侧向扩散控制的。 目前用于测量横向扩散的方法是繁琐的，耗时的，并且可能干扰。 在这个建议中，我们提出了新的技术，用于快速测量横向扩散膜使用核磁共振（NMR）光谱，非扰动技术。 这些都是改编自已建立的NMR扩散方法，但重新设计，以适应膜的独特困难。 此外，我们描述了一种新的模型膜系统，特别是通过NMR的横向扩散的研究量身定制。 这些新的核磁共振侧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求氟药物的侧向扩散，以及类胡萝卜素，一类具有独特有用的光学性质的膜结合分子。 此外，横向扩散将被测量内域诱导的寡核苷酸的类型用于基因治疗应用，并在脂筏，最近确定的膜结构的基本功能的重要性，但尚未了解从结构/动力学的观点。

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.