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

描述(申请人提供)：弹性蛋白是在各种脊椎动物组织中发现的弹性纤维的主要蛋白质。这种主要是疏水的蛋白质中的水合水平对其结构和功能起着重要的作用。许多不同组织的疾病，如心脏，已被证明与弹性蛋白的结构退化有关。提出的研究工作的总体目标是利用新颖的强脉冲梯度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空间成像是一种著名的测量样品中分子位移概率的方案。这项技术已在先前资助的项目中成功实施，以测量弹性蛋白纤维中毛孔的平均表面积与体积比。这项技术将扩展到通过对样品施加机械应力来测量限制在弹性蛋白孔隙中的水的表面张力。双量子过滤的双量子过滤核磁共振对水合重水的弹性蛋白样品，将使用定义良好的核磁共振射频脉冲序列进一步探测弹性蛋白内的局部各向异性运动。核磁共振自旋计数实验将被用来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化水中的核自旋的平均数量。这项研究的实验结果将用于测试和开发弹性蛋白的模型，以及水在其功能中的作用。这项研究所需的材料和方法利用了在核磁共振领域广为人知的脉冲序列，以及在先前资助阶段建造的硬件。这项工作的PI从研究生学习、博士后工作以及在约克学院担任初级教员的头两年，在此类实验工作中拥有丰富的经验。这些实验将利用两个已经存在的核磁共振磁铁和光谱仪，这些磁铁和光谱仪具有固态功能，可在大学校园内使用。项目简介这项研究工作试图调查有关弹性蛋白的性质和行为的基本知识，弹性蛋白是一种生物聚合物，可以赋予许多脊椎动物组织弹性。众所周知，这种生物聚合物的弹性与水合作用有关，这一努力的目的是表征生物聚合物中水的动态。该提案非常符合国家卫生研究所的总体目标，即对生命系统的性质和行为进行基础研究，以延长健康寿命，减轻疾病和残疾的负担。

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.