Elucidating Fundamental Factors Driving Self-assembly with Guided Interactions in Multicomponent Enzyme Systems Using Model Nanostructured Platforms

在化学系的大分子、超分子和纳米化学计划和既定的刺激竞争研究计划(EPSCoR)的支持下，堪萨斯大学的辛迪·L·贝里教授和坎丹·塔默勒教授正在研究控制生物分子在界面上组装和组织的因素。亲和肽标签将被用于选择性地引导包括酶在内的生物分子在材料表面的自组装，以创建在纳米尺度上组织的多组分生物活性材料。正在开发的金属纳米结构平台旨在了解材料特性、曲率、间距和大小对生物分子空间组织自组装的作用。该项目将使生物混合材料能够模仿大自然为复杂任务而进化出的精致功能，这将使增强的生物传感、生物催化和生物燃料应用成为一种替代能源。在实施该项目的过程中，研究生和本科生将接受纳米科学、生物分子和生物材料日益融合的培训。此外，研究团队将通过参加工程博览会和化学嘉年华活动，以及制定“科学之夜”计划，在早期阶段让学生参与科学活动，向堪萨斯大学社区和当地中小学开展外联和服务。在参与该项目的学生的参与下，将进行纳米光刻和成像的公开演示。该项目的重点是利用模型纳米结构平台探索多酶系统在多肽引导下自组装的基本因素，以利用它们的协调活动。大自然巧妙地组织了一级级联的酶来协同工作；然而，由于控制功能组装的因素的复杂性和缺乏信息，人工组装这种复杂系统的尝试受到了阻碍。从生物催化到生物传感，到能源收集和生物燃料的新兴应用可能受益于具有级联活性的偶联酶的组装，因此阐明控制这种复杂体系组装的因素将具有广泛的应用。具体地说，将使用光学显微镜和原子力显微镜以及生物活性分析来研究多肽标签、多肽标记的酶和偶联酶对的共同组装，以确定组装的生物分子的分布、构象和取向，以及金属纳米结构的组成、间距、大小和曲率如何影响这些。这项工作的科学影响更广泛，包括为生物传感和生物催化应用开发生物杂化材料的设计原则。在纳米生物材料领域的劳动力发展和社区外展方面也有重要的因素。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Macromolecular, Supramolecular and Nanochemistry program in the Division of Chemistry and the Established Program to Stimulate Competitive Research (EPSCoR), Professors Cindy L. Berrie and Candan Tamerler at the University of Kansas are investigating factors that govern the assembly and organization of biomolecules at interfaces. Affinity peptide tags will be used to selectively direct the self-assembly of biomolecules, including enzymes, onto material surfaces to create multicomponent bioactive materials organized at the nanoscale. The metal nanostructure platforms being developed are designed to enable an understanding of the role of material specificity, curvature, spacing, and size on the spatially organized self-assembly of biomolecules. The project will allow biohybrid materials to mimic the exquisite functionality nature has evolved for complex tasks, which will enable enhanced biosensing, biocatalysis and biofuel applications as an alternative energy source. In the course of conducting the project, graduate and undergraduate students will be trained in the growing convergence of nanoscience, biomolecules and biomaterials. In addition, the research team will carry out outreach and services to the community at the University of Kansas and local middle and elementary schools through participation in the Engineering EXPO and the Carnival of Chemistry events and the development of the “Science Night” program to engage students in science at an early stage. Public demonstrations on nanolithography and imaging will be conducted with the involvement of the students working on the project. The project focuses on exploring the fundamental factors responsible for peptide guided self-assembly of multi-enzyme systems using model nanostructured platforms to harness their coordinated activity. Nature exquisitely organizes cascades of enzymes to work in tandem; however, attempts to artificially assemble such complex systems are hampered by the complexity and lack of information about the factors governing functional assembly. Emerging applications from biocatalysis to biosensing, to energy harvesting and biofuels would likely benefit from assembly of coupled enzymes with cascade-like activity, and therefore elucidating the factors controlling the assembly of such complex systems would have wide ranging applications. Specifically, the assembly of peptide tags, peptide-labeled enzymes, and the co-assembly of coupled enzyme pairs will be investigated using optical and atomic force microscopy as well as bioactivity assays to determine the distribution, conformation, and orientation of assembled biomolecules and how these are affected by the metal nanostructure composition, spacing, size, and curvature. The scientific broader impacts of the work include the development of design principles for biohybrid materials for applications in biosensing and biocatalysis. There are also important elements of workforce development in the area of nanobiomaterials and of outreach the community.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.