Biomolecular Materials: Structure, Phase Behavior, & Interactions

ID：MPS/DMR/BMAT(7623)0803103 PI：Safinya，Cyrus ORG：California-Santa Barbara标题：生物分子材料：结构、相行为和相互作用内部优点：该项目旨在阐明源自轴突细胞骨架和曲率稳定脂结构的细丝状神经细丝自组装的结构和相互作用的性质。该方案将同步加速器小角X射线散射(SAXS)、光学和低温电子显微镜实验与统计力学理论研究相结合。一系列拟议的实验侧重于了解由纯化蛋白质重组的神经细丝网络中细丝间相互作用的性质。神经细丝由三种均聚物组成：神经丝-L、神经丝-M和神经丝-H。皮？S实验室的最新初步数据表明，与由核因子-M或核因子-H组成的侧武器之间的丝间相互作用具有本质上的不同行为。利用同步加速器SAXS-渗透压技术，提出了一系列的直接力测量方法，与互补的相行为研究相结合，将导致对神经细丝之间相互作用的本质的全面理解。研究将在二元(核因子-1H、核因子-1M)和三元(核因子-LMH)混合物中作为侧臂接枝密度的函数在核素凝胶相中进行。S小组将对模拟核因子-L、核因子-M和核因子-H侧臂结构的聚两性离子刷之间的相互作用进行统计力学研究。另一组拟议的实验是基于PI最近发现的由膜曲率稳定的多价脂类导致的嵌段脂质体。低温电子显微镜显示，这些块状物由形状独特的纳米球、梨子、管子或棒子组成。事实上，为了特定的细胞功能而在体内发生的类似的膜形状变化，通常是由膜和曲率稳定蛋白之间的相互作用引起的。通过使用Pi？S小组定制合成的一系列脂类，允许曲率稳定脂的形状、大小和电荷的系统变化(模仿更复杂的曲率稳定蛋白的性质)，拟议的实验将允许PI区分电荷和脂类形状对嵌段脂质体形成的单独贡献。Broader的影响：从更广泛的角度来看，除了进一步加强我们对聚电解质刷子的理解(这在实验和理论上仍然知之甚少)，这项研究还应该加强对轴突细胞骨架的结构和相互作用的理解。在嵌段脂质体的研究中观察到的纳米棒和纳米管在模板(例如，生产纳米线)或化学输送领域具有潜在的应用。拟议的生物分子材料项目是多学科的，要求PI教育和培训本科生和研究生，以及博士后研究人员现代方法论，以解决物理、化学、工程和生物学之间的重要问题。皮？S集团开发的最先进的表征能力集成在加州大学伯克利分校材料研究科学与工程中心(MRSEC)的X射线设施中，并向来自整个园区的30多个小组组成的非常广泛的用户群开放。学生还可以熟悉现有的国家研究设施。非政府组织和共同非政府组织积极参与UCSB与圣巴巴拉以外的社区学院和大学的外联方案，鼓励代表人数不足的群体参与。这些计划包括：MRSEC扩展计划、纳米系统科学与工程技术(INSET)实习扩展计划和教师研究经验(RET)扩展计划。这些项目允许私人投资机构对本科生和高中教师进行多学科科学和工程方法的培训和教育。

ID: MPS/DMR/BMAT(7623) 0803103 PI: Safinya, Cyrus ORG: California-Santa BarbaraTitle: Biomolecular Materials: Structure, Phase Behavior, and InteractionsINTELLECTUAL MERIT: The project aims to elucidate the nature of structures and interactions in self-assemblies of filamentous neurofilaments derived from the axonal cytoskeleton and structures of curvature stabilizing lipids. The proposal combines synchrotron small angle- x-ray-scattering (SAXS), optical and cryo-electron electron microscopy experiments with statistical mechanical theoretical investigations. One series of proposed experiments focuses on understanding the nature of interfilament interactions in neurofilament networks reconstituted from purified proteins. Neurofilaments (NFs) consist of three homopolymers NF-L, NF-M, and NF-H. Recent preliminary data from the PI?s laboratory suggest 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 gel phases as a function of sidearm grafting densities in binary (NF-LH, NF-LM), and ternary (NF-LMH) mixtures. The co-PI?s group will carry out statistical mechanical studies of interactions between polyampholyte brushes mimicking the NF sidearm structure of NF-L, NF-M, and NF-H. Another set of proposed experiments is based on the PI's recent discovery of block liposomes resulting from membrane curvature stabilizing multivalent lipids. Cryogenic-TEM revealed the blocks to consist of distinctly shaped nanoscale spheres, pears, tubes, or rods. Indeed, similar membrane shape changes, occurring in vivo for the purpose of specific cellular functions, are often induced by interactions between membranes and curvature stabilizing proteins. By employing a series of lipids custom synthesized in the PI?s group, which allow for systematic variations in the shape, size and charge of the curvature stabilizing lipids (mimicking properties of more complex curvature stabilizing proteins), the proposed experiments will permit the PI to distinguish between the separate contributions of charge and lipid shape responsible for the formation of block liposomes.BROADER IMPACTS: From a broader perspective, aside from further enhancing our understanding of polyelectrolyte brushes (which remains poorly understood, both in experiment and theory), the research should enhance the understanding of structures and interactions of the axonal cytoskeleton. The nanorods and nanotubes observed in the studies of block liposomes have potential applications in the area of templating (e.g. to produce nanowires) or chemical delivery. The proposed biomolecular materials program is multidisciplinary and obligates the PIs to educate and train undergraduate and graduate students, and postdoctoral researchers in modern methodologies required to address important problems at the interface between physics, chemistry, engineering, and biology. The state-of-the-art characterization capabilities developed in the PI?s group are integrated within the UCSB Materials Research Science and Engineering Center (MRSEC) x-ray facility and open to a very wide user base comprised of over 30 groups from across campus. Students also gain familiarity with existing national research facilities. The PI and co-PI actively participate in UCSB Outreach Programs with the community colleges and colleges and universities outside of Santa Barbara, which encourage participation by under-represented groups. These programs include, the MRSEC outreach program, the Internships in Nanosystems Science and Engineering Technology (INSET) outreach program, and the Research Experience for Teachers (RET) outreach program. These programs allow the PIs to train and educate undergraduate students and high school teachers in multidisciplinary methods of science and engineering.