Probing dynamics of water in elastin by q-space imaging and multiple quantum NMR

描述（申请人提供）：弹性蛋白是存在于各种脊椎动物组织中的弹性纤维的主要蛋白质。已知这种主要疏水蛋白的水合水平在其结构和功能中起重要作用。许多不同组织的疾病，如心脏，已被证明与弹性蛋白的结构降解有关。该研究的主要目的是利用新型强脉冲梯度q空间核磁共振成像、自旋计数核磁共振和氘双量子过滤核磁共振研究来研究水在弹性蛋白结构和功能中的作用。q空间成像是测量样品中分子位移概率的一种众所周知的方案。该技术已成功应用于先前资助的项目中，用于测量弹性蛋白纤维中孔隙的平均表面体积比。该技术将扩展到测量水的表面张力限制在弹性蛋白的孔隙通过机械应力样品。双量子过滤核磁共振在氘水合弹性蛋白样品将进一步探测局部各向异性运动在弹性蛋白使用一个明确定义的核磁共振射频脉冲序列。核磁共振自旋计数实验将用于测量由于部分平均偶极相互作用的存在而聚集在弹性蛋白周围水合水中的核自旋的平均数量。本研究的实验结果将用于测试和开发弹性蛋白模型，以及水在其功能中的作用。本研究所需的材料和方法借鉴了核磁共振界众所周知的脉冲序列，以及在先前资助阶段建立的硬件。该项目的负责人在这类实验工作方面有着丰富的经验，包括研究生学习、博士后工作以及他在约克学院担任初级教员的头两年。实验将使用两个已经存在的核磁共振磁体和具有固态能力的光谱仪，这些仪器可以在大学校园内获得。本研究旨在调查弹性蛋白的性质和行为的基础知识，弹性蛋白是一种赋予许多脊椎动物组织弹性的生物聚合物。这种生物聚合物的弹性已知与水合作用有关，研究的目的是表征水在生物聚合物中的动力学。该提案完全符合美国国立卫生研究院的总体目标，即对生命系统的性质和行为进行基础研究，以延长健康生命，减少疾病和残疾的负担。

DESCRIPTION (provided by applicant): Elastin is the main protein of the elastic fiber found in various vertebrate tissues. The hydration level in this mainly hydrophobic protein is known to play an important role in its structure and function. Many diseases of various tissues, such as the heart, have been shown to be correlated to structural degradation of elastin. The broad objective of the proposed research effort is to investigate the role of water in the structure and function of elastin using novel strong pulse gradient q-space Nuclear Magnetic Resonance (NMR) imaging, spin counting NMR and deuterium double quantum filtered NMR studies. Q-space imaging is a well known scheme for measuring the probability of molecular displacement in a sample. This technique was successfully implemented in the previously funded project to measure the average surface- to-volume ratio of pores in elastin fibers. The technique will extended to measuring the surface tension of water confined in pores of elastin by mechanically stressing a sample. Double Quantum Filtered NMR on deuterium- hydrated elastin samples will further probe local anisotropic motion within elastin using a well defined NMR radiofrequency pulse sequence. NMR spin counting experiments will be used to measure the average number of nuclear spins that are clustered in the waters of hydration surrounding elastin due to the presence of a partially averaged dipolar interaction. The experimental findings of this study will be used to test and develop models of elastin, and the role of water in its function. The materials and methods necessary for this study draw upon pulse sequences well-known in the NMR community, as well as hardware that was built in the previously funded stage. The PI of the effort has a significant amount of experience in such experimental work from graduate studies, postdoctoral work and from his first two years as a junior faculty member at York College. The experiments will make use of two already existing NMR magnets and spectrometers with solid- state capabilities that are available on the college campus. PROJECT NARRATIVE This research effort seeks to investigate fundamental knowledge about the nature and behavior of elastin, a biopolymer that that confers elasticity to many vertebrate tissues. The elasticity of this biopolymer is known to be correlated to hydration, and the aim of the effort is to characterize the dynamics of water in the biopolymer. The proposal fits well within the overall goals of the National Institute of Health for fundamental research into the nature and behavior of living systems for extending healthy life and reducing the burdens of illness and disability.