3D Organized Nanoscale Reactors

非技术摘要：生物体中的生化反应以及许多传感和制造应用中的生化反应是由一种特殊类型的生物分子--酶控制的。虽然设计具有更高性能的新型酶的需求很大，但这是一项非常具有挑战性的任务，需要巨大的计算和合成努力。还有另一种方法可以增强酶的化学活性，并允许更方便地使用它们--将这些生物分子包装在阵列中。这种包装还开启了处理和加工酶的可能性，类似于传统材料。到目前为止，酶阵列是通过将酶连接到表面来形成的。这些涂有酶的表面用于生物传感以提高灵敏度，这要归功于表面上的酶比溶液中的酶密度高得多。它们对工业化学合成也非常有用，因为它们能够增强反应，而且它们可以很容易地集成到制造过程中。然而，目前制备这种酶阵列的方法仅限于基于表面的形式。这项拟议的研究旨在建立一种概念上不同的方法，以块状材料而不是表面的形式创建三维(3D)酶阵列。所提出的方法提供了对3D酶阵列的空间排列和组成的纳米级控制。这种阵列代表了一类新的化学材料，具有可定制的结构，并具有可调节和增强的反应活性。该计划旨在解决创造这些新的酶材料的两个关键问题：如何在3D结构控制下合成具有化学活性的材料，以及如何通过使用新型3D阵列来提高酶的化学性能。这项拟议的研究旨在建立设计的化学纳米材料领域的转化能力，这些材料在生物传感、反应管理和化学合成方面具有潜在的应用。技术摘要：通过纳米尺度控制单个酶的放置，以三维(3D)方式组织酶和酶级联的能力可以为创造化学活性材料和调节反应途径开辟新的途径。然而，建立这样的能力是一个巨大的挑战。该提案寻求开发一种通用的方法来对酶的组装进行编程，在DNA框架的指导下，将其组装成量身定制的3D有序纳米反应器阵列，并控制晶格类型、单元细胞间距、单个酶的比例以及化学活性材料的相对布局。拟议的研究将酶的结构组织的新水平和酶的级联应用到所需的3D组织中。利用酶的级联模型，这项研究将探索3D网络中的催化，以及通过控制酶的局部化学环境和纳米反应器阵列的全局结构来修饰催化的效果。该研究计划将把合成DNA-酶模块及其组装成3D材料的努力与形成的阵列的结构和化学分析结合起来，以探索新的3D催化网络。将探索酶的大规模、3D组织和通过3D阵列的分子传输的简易性所产生的协同网络效应。该计划的主要目标包括：(I)对3D纳米反应器阵列进行量身定制的控制；(Ii)在3D中确定酶-DNA整合和酶共定位引起的局部效应；(Iii)开发对制造酶材料的完全空间控制，例如纳米级阵列的晶体系统、酶之间的间距、酶的比例以及阵列内级联的纳米级组织。这项研究旨在建立合成新型3D纳米反应器阵列的新方法，阐明网络化学反应的结构-功能关系，并开发操纵化学路径的方法。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。

Non-Technical Abstract: Biochemical reactions in organisms and in numerous sensing and manufacturing applications are controlled by a special type of biomolecule, the enzyme. While there is a great demand for the design of new types of enzymes with enhanced properties, it is a very challenging task that requires enormous computational and synthetic efforts. There is another way to enhance the chemical activity of enzymes and to allow for a much more convenient use of them - by packaging these biomolecules in arrays. Such packaging also opens up the possibility of handling and processing enzymes similar to conventional materials. Until now, enzymatic arrays have been formed by attaching enzymes to surfaces. These enzyme-coated surfaces are used in biosensing to boost sensitivity, thanks to a much higher density of enzymes on a surface relative to in solution. They are also extremely useful for industrial chemical synthesis due to their ability to enhance reactions and how easily they can be integrated into the manufacturing processes. However, current methods to fabricate such enzymatic arrays are limited to surface-based forms. The proposed research aims to establish a conceptually different approach to create three-dimensional (3D) enzymatic arrays in the form of a bulk material rather than a surface. The proposed approach offers nanoscale control over the spatial arrangement and composition of 3D enzymatic arrays. Such arrays represent a new class of chemical materials with tailorable structure, and with modulated and enhanced reactivity. The proposed program seeks to address two key questions in creating these new enzymatic materials: how to synthesize the chemically active materials with control of their structure in 3D, and how to improve the chemical performance of enzymes through the use of novel 3D arrays. The proposed research aims to establish transformative capabilities in the area of designed chemical nanomaterials with potential applications in biosensing, reaction management, and chemical synthesis. Technical Abstract: The ability to organize enzymes and enzymatic cascades in three-dimensions (3D) with a nanoscale control over the placement of individual enzymes can open new routes for creating chemically active materials and modulating reaction pathways. However, establishing such capabilities presents a significant challenge. The proposal seeks developing a versatile methodology to program assembly of enzymes, guided by DNA frames, into tailored 3D ordered arrays of nanoreactors with control over lattice type, unit cell spacing, ratio of individual enzymes, and relative layout of the chemically active materials. The proposed studies will apply new levels of structure organization of enzymes and enzymatic cascades into desired 3D organizations. Using model enzymatic cascades, the research will explore catalysis within a 3D network and effects of its modification by controlling local chemical environments of enzymes and a global structuring of nanoreactor arrays. The research program will integrate efforts in synthesis of DNA-enzyme modules and their assembly into 3D materials with structural and chemical analysis of formed arrays for exploration of the novel 3D catalytic networks. Synergistic network effects stemming from large scale, 3D organization of enzymes and ease of molecular transport though 3D arrays will be explored. The major objectives of the program include: (i) tailored control over 3D nanoreactor arrays; (ii) determination of local effects arising from enzyme-DNA integration and enzyme colocalizations in 3D; (iii) development of full spatial control over fabrication enzymatic materials, such as crystal system of nanoscale arrays, inter-enzyme spacing, ratio of enzymes, and nanoscale organization of cascades within arrays. The research aims to establish new methods for synthesis of novel classes of 3D nanoreactor arrays, to elucidate the structure-function relationship of networked chemical reactions and to develop ways for manipulating chemical pathways.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.