SYNCHROTRON X-RAY STUDIES OF BIOMOLECULAR MATERIALS

生物分子材料的同步辐射 X 射线研究

• 批准号: 8170193
• 负责人: CYRUS R SAFINYA
• 金额: $ 0.85万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170193
• 关键词: Amyotrophic Lateral Sclerosis; Axon; Behavior; Biopolymers; Cattle; Charge; Computer Retrieval of Information on Scientific Projects Database; Cytoskeleton; Data; Dendrites; Filament; Funding; Gel; Grant; Institution; Knowledge; Measurement; Microtubules; Motor Neuron Disease; Nature; Neuraxis; Neurofilament-H; Neurofilament-L; Neurofilament-M; Neurons; Osmotic Pressure; Phase; Play; Process; Research; Research Personnel; Resources; Role; Series; Source; Structure; Synchrotrons; Techniques; United States National Institutes of Health; density; in vivo; neurofilament; reconstitution; research study; scaffold

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The proposed experiments aim to elucidate the nature of structures and interactions in reconstituted assemblies of filamentous neurofilaments (NFs) derived from neurons of the bovine central nervous system. NFs form networks in neurons, which are believed to play a key role both in the structural stability of neuronal processes (axons and dendrites) and as scaffolds for microtubules dispersed throughout the cytoskeleton of the processes. Neurofilaments consist of three homopolymers NF-L, NF-M, and NF-H, assembled in varying composition to form the mature NF filament with protruding C-terminus sidearms. However, the nature of the interfilament interactions and the precise role of each homopolymer within the network remain unclear. In mature neurons the composition of the three NF fractions is regulated over a narrow range with deviations in composition resulting in the disruption of the NF-network (hypothesized to be due to incorrect sidearm interactions) and motor neuron diseases (e.g. amyotrophic lateral sclerosis, Lou Gehrig?s disease). Thus, it is important to understand the role of distinct sidearms in imparting stability to the network through sidearm-sidearm interactions. Our recent synchrotron SAXS data suggests qualitatively different behavior for interfilament interactions with sidearms consisting of either NF-M or NF-H. Using the synchrotron SAXS-osmotic pressure technique, a series of direct force measurements are proposed, which when combined with complementary phase behavior studies, should result in a comprehensive understanding of the nature of the interactions between neurofilaments. The studies will be conducted in NF gels as a function of sidearm densities in binary (NF-LH, NF-LM), and ternary (NF-LMH) mixtures mimicking in-vivo conditions. Aside from further enhancing our knowledge of charged biopolymer networks, the experiments should enhance the understanding of structures and interactions within the axonal cytoskeleton.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 提出的实验旨在阐明源自牛中枢神经系统神经元的丝状神经丝（NFS）的结构和相互作用的性质。 NFS在神经元中形成网络，据信它们在神经元过程（轴突和树突）的结构稳定性中都起着关键作用，并且是微管的支架，分散在整个过程的细胞骨架中。神经丝由三个均聚物NF-L，NF-M和NF-H组成，它们以不同的组成组成，以形成成熟的NF丝与突出的C末端侧臂。然而，灌输相互作用的性质以及每个均聚物在网络中的确切作用尚不清楚。在成熟的神经元中，三个NF级分的组成在狭窄范围内受到调节，并且组成偏差会导致NF网络的中断（假设是由于侧臂相互作用不正确而导致的）和运动神经元疾病（例如，疗效的后期sclerisos，lou Gehrig？sisteral sisterasis sisterasis，lou Gehrig？s病）。因此，重要的是要了解不同的侧臂在通过侧s-sitearm相互作用向网络传授稳定性中的作用。我们最近的同步加速器SAXS数据表明，与由NF-M或NF-H组成的侧膜相互作用的界面相互作用的质量不同。使用同步加速器SAXS-渗透压力技术，提出了一系列直接测量值，当与互补相行为研究结合使用时，应全面了解神经丝之间相互作用的性质。这些研究将在NF凝胶中与二元密度（NF-LH，NF-LM）和三元（NF-LMH）混合物中的二元密度一起进行。除了进一步增强我们对带电的生物聚合物网络的了解外，实验还应增强对轴突细胞骨架内结构和相互作用的理解。