Collaborative Research: Comparative Studies of Pleated beta-Sheet and Rippled beta-Sheet Peptide Nanofibrils

有了这个奖项，化学系的大分子、超分子和纳米化学项目将资助罗切斯特大学的Bradley L. Nilsson博士和新泽西理工学院的Cristiano Dias博士研究促进β -片肽组装的结构和分子驱动力。多肽是自然产生的生物分子，存在于所有生物体中。在细胞中，它们执行许多生物功能，例如充当激素。-片是与许多人类疾病相关的肽组装中发现的常见结构，其中最值得注意的是阿尔茨海默病。在这项工作中，利用互补的实验和计算技术研究了互为镜像的两个肽的共组装。这些努力可能对分子尺度的相互作用提供关键的见解，这些相互作用决定了天然和人工β -片的组装。本研究可以简化和指导合理设计和合成具有精确组织的肽的下一代纳米材料。与这项工作相关的外展活动包括在两个机构开展的一门基于探究的水凝胶迷你课程，名为“凝胶或不凝胶：黏液科学”。此外，这两个研究团队还会在夏季为高中实习生提供为期六周的指导，以提高他们对科学研究和化学科学的兴趣。这项工作可能会带来重大的社会效益，因为它有可能提供有关β -薄片自组装的疾病机制的见解，例如阿尔茨海默病和淀粉样变性。本研究的重点是获得对L-和d -肽序列共同组装成波纹状纳米原纤维的结构和分子力的基本理解。这使得合理设计新的肽序列能够形成波纹状纳米纤维系统。在第一个目标中，采用互补的实验和理论方法来表征折叠β片和波纹β片纳米原纤维的比较结构。第二个目标利用理论在计算导向的评估和设计波纹β -片纳米原纤维从L-和d -肽序列。所获得的知识可能不仅适用于这些特定的材料，而且还适用于理解β -片结构在淀粉样蛋白自组装和蛋白质折叠中的作用。这项工作可能会带来重大的社会效益，因为它有可能提供有关β -薄片自组装的疾病机制的见解，例如阿尔茨海默病和淀粉样变性。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry is funding Dr. Bradley L. Nilsson from University of Rochester and Dr. Cristiano Dias from New Jersey Institute of Technology to study the structure and molecular driving forces promoting the assembly of beta-sheet peptides. Peptides are naturally occurring biological molecules that are found in all living organisms. In cells, they perform many biological functions, for example acting as hormones. Beta-sheets are a common structure found in peptide assemblies associated with many human diseases, most notable of which is Alzheimer's disease. In this work, co-assembly of two peptides that are mirror images of one another is studied using complementary experimental and computational techniques. These efforts may provide critical insight into the molecular-scale interactions that dictate the assembly of both natural and artificial beta-sheets. The this research could simplify and guide efforts to rationally design and synthesize the next generation of nanomaterials with peptides that are precisely organized. Outreach activities associated with this work includes an inquiry based mini-course on hydrogels called "To Gel or Not To Gel: The Science of Slime" which is conducted at both institutions. Additionally, the two research teams host high school interns for six weeks during the summer to provide mentoring and increase interest in scientific research and chemical sciences in general. This work may provide significant societal benefits because it has the potential to provide insight into disease mechanisms that involve beta-sheet self-assembly, such as in Alzheimer's disease and amyloidosis in general.This research focuses on obtaining fundamental understanding of the structure and molecular forces driving the co-assembly of L- and D-peptides sequences into rippled beta-sheet nanofibrils. This enables the rational design of new peptide sequences that can form rippled beta-sheet nanofibril systems. In the first objective, complementary experimental and theoretical methods are used to characterize the comparative structures of pleated beta-sheet and rippled beta-sheet nanofibrils. The second objective exploits theory in the computationally-directed assessment and design of rippled beta-sheet nanofibrils from L- and D-peptide sequences. The knowledge obtained may be applicable not only to these specific materials, but also to understanding the role of beta-sheet structures in amyloid self-assembly and in protein folding in general. This work may provide significant societal benefits because it has the potential to provide insight into disease mechanisms that involve beta-sheet self-assembly, such as in Alzheimer's disease and amyloidosis in general.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.