Instrumentation Development on Multi-Scaled Scattering for Bio-Molecular Solution

描述（由申请人提供）：本提案旨在将新开发的互相关光散射能力与同步加速器X射线散射相结合，专门设计用于生物大分子凝胶、溶液和悬浮液。结合X射线和激光散射技术将能够在连续和非常宽的空间范围（0.1 - 2000 nm）内检测结构变化和动态，即使在混浊介质中也是如此。许多生物大分子流体在经历结构变化或化学反应以及相变时会变得不透明。因此，多重散射成为一个严重的问题，特别是在可见光波长范围内。互相关技术可以在相对混浊的介质中提取单次散射信息，动态互相关函数分析产生关于物种的扩散和旋转运动的知识以及尺寸分布的估计。这些信息，当同时结合X射线散射和衍射结果，是无法获得的方法，如NMR或显微镜。用于复杂生物大分子溶液研究和教育的独特多尺度散射仪器将包括广角X射线衍射（WAXD，空间分辨率0.1-2 nm）、小角X射线散射（SAXS，空间分辨率2-120 nm）和具有互相关的激光散射（空间分辨率5-2000 nm）的集成。实验将包括胶原蛋白中的体外生物矿化、肌肉伸展、生物大分子聚集体的溶液行为，例如，淀粉样蛋白-与阿尔茨海默病有关的Abeta 42肽;受精过程中来自fertilinD和cyritestin的肽。拟议的光散射仪器，包括一个“恒定浓度”流动池（用于生物矿化研究）和一个小容量溶液池（用于珍贵生物材料），将在斯托尼布鲁克组装和初步测试，然后纳入布鲁克海文国家实验室（BNL）国家同步加速器光源（NSLS）的X27 C光束线。该仪器将是世界上第一个将激光与互相关和X射线散射相结合的仪器。该仪器将为本提案中描述的几个NIH项目提供目前无法获得的新信息;通过X27 C光束线的一般用户，它也将对许多其他NIH资助的项目有用。

DESCRIPTION (provided by applicant): The present proposal is aimed at incorporating the newly developed cross-correlation light scattering capability with synchrotron X-ray scattering, specifically designed for bio-macromolecular gels, solutions and suspensions. The combined X-rays and laser light scattering techniques will be able to detect structural variations and dynamics in a continuous and very broad spatial range (0.1 - 2000 nm), even in turbid media. Many bio-macromolecular fluids, when undergoing structure changes or chemical reactions as well as phase transitions, can become opaque. Then, multiple scattering becomes a serious problem, especially in the visible light wave length range. The cross-correlation technique can extract single-scattering information in relatively turbid media, with the dynamic cross-correlation function analysis yielding knowledge on diffusive and rotational motions of species and estimates of size distributions. Such information, when simultaneously combined with X-ray scattering and diffraction results, is not attainable by methods such as NMR or microscopy. The unique multiple-scaled scattering instrumentation for research and education of complex bio- macromolecular solutions will include the integration of wide-angle X-ray diffraction (WAXD, spatial resolution 0.1-2 nm), small-angle X-ray scattering (SAXS, spatial resolution 2-120 nm) and laser light scattering with cross-correlation (spatial resolution 5-2000 nm). Experiments will include in-vitro bio- mineralization in collagen, muscle extension, solution behavior of bio-macromolecular aggregations, e.g., amyloids - the Abeta42 peptide involved in Alzheimer's disease; peptides derived from fertilinD and cyritestin in fertilization. The proposed light-scattering instrumentation, including a "constant-concentration" flow cell (for bio-mineralization study) and a small-volume solution cell (for precious bio-materials), will be assembled and initially tested at Stony Brook, and then incorporated into the X27C beam line in the National Synchrotron Light Source (NSLS), Brookhaven National Laboratory (BNL). The proposed instrumentation will be the first of its kind for combined laser light with cross-correlation and X-ray scattering research in the world. This instrumentation will provide new information, not accessible today, to several NIH projects described in this proposal; it will also be useful to many other NIH funded projects through general users of the X27C beamline.