Nano-Reactor Assembly Across Multiple Lengthscales

非技术性：该奖项由材料研究部的生物材料项目授予印第安纳大学，旨在利用生物过程和定向自组装来制造新一代材料，以克服其局限性。这位研究人员认为，生物细胞是设计新的复杂材料的灵感来源，这种材料由许多不同长度的分子组成。目前，即使是最简单的生命系统也表现出远远超出了合成模仿能力的复杂性。生物细胞对环境压力的反应能力在于它们调节酶介导的反应的生化网络的能力。利用酶的力量和复杂性以及酶网络来合成开发复杂的催化材料尚未实现，部分原因是酶的脆弱性及其与材料加工方法的不兼容。该项目将制定一套设计规则，将材料特性和催化功能纳入生物灵感材料。这位研究人员预计，这些材料将在生物设计的催化领域产生影响，它们的利用将导致更节能、可再生、安全和负担得起的技术的发展。作为该项目不可分割的一部分，这位研究人员将继续开发科学推广方案，在这些方案中，参与尖端科学的本科生和研究生也将学习如何有效地向公众交流他们的研究并激励下一代科学家。这将通过与当地和地区学校的伙伴关系来实现，在这些学校中，教师、学生和研究人员之间的长期关系可以培养人们对科学的兴奋，并与青年和在科学中代表不足的社区建立联系。技术：使用生物灵感的方法，这位研究人员将开发一种复杂的自组装系统来创建蛋白质笼结构，其中最多3种酶的多个副本通过受控的邻接和化学计量进行封装。这些酶进行了一系列耦合的反应，创造了一种能够影响甲醇(以及潜在的甲烷)氧化的合成代谢途径的材料。此外，基于中间体在配对酶之间的扩散长度，建立了预测共局域条件下偶联反应动力学的数学模型。计划中的动力学研究表明，序列酶之间的中间通道既取决于酶间的距离，也取决于两种酶的动力学参数之间的平衡，这一发现挑战了简单的观点，即任何共定位都会自动产生增强的整体活性。此外，单个纳米反应器颗粒可以组装成有序的分层阵列，为从单个蛋白质笼构建的具有复杂催化性能的大宗材料的程序化组装提供了一条前进的道路。因此，使用自然产生的和设计的分子组件，研究人员将通过在多个长度尺度上定向自组装模块化构件来构建复杂的催化活性材料。本研究背景下的研究生培训将包括：使用冷冻电子显微镜和图像重建进行结构研究，以评估酶在自组装蛋白质笼结构中的堆积情况；质谱分析，以评估拥挤效应引起的酶动力学的变化；动态和静态(多角度)光散射，以评估从分子组件到材料的自组装过程；小角X射线散射(Argonne National Lab(APS)和Brookaven National Lab(NSLS II))，以探索蛋白质笼材料组装中的长程有序性。学生们将接受相关的人物塑造技术培训。

Non-technical: This award by the Biomaterials program in the Division of Materials Research to University of Indiana is to use biological processes and directed self-assembly to make a new generation of materials to overcome their limitations. The investigator sees the biological cell as an inspiration for the design of new complex materials, assembled from molecular components across many different length scales. Currently, even the simplest living systems exhibit complexity that is well beyond the ability to mimic synthetically. The power of biological cells to respond to environmental stress lies in their ability to regulate biochemical networks of enzyme-mediated reactions. Harnessing the power and complexity of enzymes, and enzyme networks, for the synthetic development of complex catalytic materials has not been realized in part due to the fragility of enzymes and their incompatibility with materials processing approaches. This project will develop a set of design rules to incorporate materials properties and catalytic functions to bioinspired materials. This researcher expects these materials to make impacts in areas of bio-designed catalysis and that their utilization will lead to the development of more energy-efficient, renewable, safe and affordable technologies. As an integral part of the project, this investigator will continue to develop science outreach programming wherein undergraduate and graduate students, participating in cutting-edge science, will also learn to effectively communicate their research to the general public and inspire the next generation of scientists. This will be achieved through partnerships with local and regional schools in which long-term relationships between teachers, students, and researchers can foster an excitement about science and connect with youth and communities that are underrepresented in the sciences.Technical: Using a bioinspired approach, this researcher will develop a complex self-assembling system to create protein cage architectures in which multiple copies of up to 3 enzymes are encapsulated with controlled adjacency and stoichiometry. These enzymes perform a coupled cascade of reactions, creating a material capable of effecting a synthetic metabolic pathway for methanol (and potentially methane) oxidation. In addition, a mathematical model is developed for predicting the kinetics for coupled reactions under co-localized conditions, based on the diffusion length of intermediates between partner enzymes. The planned kinetic studies showed that intermediate channeling between sequential enzymes is dependent on both the inter-enzyme distance as well as a balance between the kinetic parameters of the two enzymes, a finding that challenges the simplistic view that any co-localization will automatically yield enhanced overall activities. In addition, individual nanoreactor particles can be assembled into ordered hierarchical arrays providing a path forward for the programmed assembly of bulk materials built from individual protein cages and having designed complex catalytic properties. Thus, using naturally occurring and designed molecular components, the investigator will construct complex catalytically active materials through directed self-assembly of modular building blocks at multiple lengthscales. Graduate student training in the context of this research will include: structural studies using cryo-electron microscopy and image reconstruction to evaluate the packing of enzymes within the self-assembled protein cage architectures; mass spectrometry to evaluate changes in enzyme dynamics due crowding effects; dynamic and static (multi-angle) light scattering to evaluate the self-assembly processes from molecular components to materials; small angle x-ray scattering (Argonne National lab (APS) and Brookhaven National Lab (NSLS II) to probe the long range order in the assembly of protein cage materials. The students will be trained in the relevant characterization techniques.