Collaborative Research: A biomimetic dynamic self-assembly system programmed using DNA nanostructures

合作研究：使用 DNA 纳米结构编程的仿生动态自组装系统

• 批准号: 1607854
• 负责人: Nils Walter
• 金额: $ 15万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1607854&HistoricalAwards=false
• 关键词: Collaborative; Research; biomimetic; dynamic; self

Non-technical: These collaborative awards by the Biomaterials program in the Division of Materials Research to Arizona State University (lead) and University of Michigan Ann Arbor (non-lead) are to study DNA polymerization and depolymerization to biomimic the functions of microtubules in cells. This award is co-funded by the following programs: 1) BioMaPS program in the Division of Materials Research; and 2) Biotechnology and Biochemical Engineering program in the Division of Chemical and Bioengineering, Environmental, and Transport Systems (ENG). The award will study the dynamic self-assembly and disassembly observed in cellular microtubules, which are involved in a number of cell functions such as intracellular transport, cell division, gene expression, etc. With this award, the microtubule functions will be mimicked by designing the self-assembly seen in DNA system. Scientific broader impacts of this study will be in developing biocompatible motors, robotics, and other applications such as drug and gene delivery systems. As part of the broader impact activities, this project will provide interdisciplinary training opportunities to students at the interface between DNA nanotechnology and single molecule biophysics. In addition, this project aims to engage high school students through experiential learning, providing them with teaching tools, and developing a STEM volunteer network. Finally, the single-molecular probing will be performed in the NSF-funded Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan, which has a vigorous outreach program to the broader scientific community.Technical: This project will build synthetic DNA-based assemblies that biomimic the salient features of dynamic self-assembly seen in cellular microtubules. Taking advantage of the DNA nanostructure programmability, this project aims to: investigate the kinetic determinants of interactions including cooperative binding, nucleation, and growth; mimic the treadmilling (active transport by self-assembly and disassembly) and dynamic instability of microtubules by employing driving forces intrinsic to Holliday junction isomerization with intermediate assembly stages that can be isolated and studied; and visualize and control of the treadmilling and dynamic instability of the DNA assembly line using comprehensive single-molecule characterization methods. Examination of this synthetic dynamic assembly system will lay the groundwork in the design and construction of sophisticated dynamic molecular assemblies based on DNA. Results from this project will provide a theoretical foundation for DNA-based motors, robotics, and other dynamic transport systems. These studies could in turn pave the way for assembling a DNA tile system that can directionally step on a programmed dynamic assembly line that mimics the motion of motor proteins (e.g., dynein or kinesin) seen in microtubules.

非技术：这些合作奖项由亚利桑那州立大学（牵头）和密歇根大学安娜堡分校（非牵头）材料研究部生物材料项目颁发，旨在研究DNA聚合和解聚，以模拟细胞中微管的功能。该奖项由以下项目共同资助：1)材料研究部BioMaPS项目；2)化学与生物工程、环境与运输系统（ENG）学部的生物技术与生化工程专业。该奖项将研究在细胞微管中观察到的动态自组装和拆卸，这涉及许多细胞功能，如细胞内运输、细胞分裂、基因表达等。有了这个奖项，微管的功能将通过设计DNA系统中看到的自组装来模仿。这项研究对科学的广泛影响将是开发生物相容性马达、机器人和其他应用，如药物和基因传递系统。作为更广泛的影响活动的一部分，该项目将为学生提供DNA纳米技术和单分子生物物理学之间界面的跨学科培训机会。此外，该项目旨在通过体验式学习吸引高中生，为他们提供教学工具，并建立STEM志愿者网络。最后，单分子探测将在美国国家科学基金会资助的密歇根大学实时单分子分析（SMART）中心进行，该中心对更广泛的科学界有一个积极的推广计划。技术：该项目将构建基于dna的合成组件，仿生学细胞微管中动态自组装的显著特征。利用DNA纳米结构的可编程性，该项目旨在：研究相互作用的动力学决定因素，包括合作结合、成核和生长；利用Holliday结异构化的内在驱动力，模拟微管的跑步（通过自组装和拆卸的主动运输）和动态不稳定性，并在中间组装阶段进行分离和研究；以及利用综合单分子表征方法可视化和控制DNA装配线的踩踏和动态不稳定性。对这种合成动态组装系统的研究将为基于DNA的复杂动态分子组装的设计和构建奠定基础。这个项目的结果将为基于dna的马达、机器人和其他动态运输系统提供理论基础。这些研究可以反过来为组装DNA瓦片系统铺平道路，该系统可以定向地踩在模拟微管中看到的运动蛋白（例如，动力蛋白或动力蛋白）的程序化动态装配线上。