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.

非技术性：这些由材料研究部生物材料项目授予亚利桑那州立大学（牵头）和密歇根大学安娜堡分校（非牵头）的合作奖项，旨在研究 DNA 聚合和解聚，以仿生细胞中微管的功能。该奖项由以下项目共同资助：1）材料研究部的 BioMaPS 项目； 2）化学和生物工程、环境和运输系统（ENG）部门的生物技术和生物化学工程项目。该奖项将研究细胞微管中观察到的动态自组装和分解，这些微管涉及细胞内运输、细胞分裂、基因表达等多种细胞功能。获得该奖项后，将通过设计来模仿微管功能DNA 系统中的自组装。这项研究的更广泛的科学影响将在于开发生物相容性电机、机器人以及药物和基因输送系统等其他应用。作为更广泛影响活动的一部分，该项目将为学生提供 DNA 纳米技术和单分子生物物理学交叉领域的跨学科培训机会。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，并发展 STEM 志愿者网络。最后，单分子探测将在密歇根大学 NSF 资助的实时单分子分析 (SMART) 中心进行，该中心向更广泛的科学界制定了积极的推广计划。 技术：该项目将建立基于 DNA 的合成组装体，仿生细胞微管中动态自组装的显着特征。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，包括协同结合、成核和生长；通过利用霍利迪连接体异构化固有的驱动力以及可以分离和研究的中间组装阶段，模拟微管的跑步（通过自组装和拆卸进行主动运输）和动态不稳定性；使用综合单分子表征方法对 DNA 装配线的运行和动态不稳定性进行可视化和控制。对这种合成动态组装系统的检查将为设计和构建基于 DNA 的复杂动态分子组装体奠定基础。该项目的结果将为基于 DNA 的电机、机器人和其他动态运输系统提供理论基础。这些研究反过来可以为组装DNA瓦片系统铺平道路，该系统可以定向地踏上模拟微管中运动蛋白（例如动力蛋白或驱动蛋白）运动的编程动态装配线。