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: 1607832
• 负责人: Yan Liu
• 金额: $ 27万
• 依托单位: Arizona State University
• 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=1607832&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：这些合作奖项由材料研究部的生物材料项目授予亚利桑那州立大学（牵头）和密歇根大学安阿伯（非牵头），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）部的生物技术和生物化学工程项目。该奖项将研究在细胞微管中观察到的动态自组装和拆卸，这些微管参与了许多细胞功能，如细胞内运输，细胞分裂，基因表达等。通过该奖项，微管功能将通过设计DNA系统中的自组装来模拟。这项研究的更广泛的科学影响将是开发生物相容性电机，机器人技术和其他应用，如药物和基因输送系统。作为更广泛的影响活动的一部分，该项目将提供跨学科的培训机会，在DNA纳米技术和单分子生物物理学之间的接口的学生。此外，该项目旨在通过体验式学习，为高中生提供教学工具，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单分子实时分析（SMART）中心进行，该中心对更广泛的科学界有着积极的推广计划。技术：该项目将构建基于合成DNA的组装体，仿生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，本项目的目标是：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;模拟纳米铣削，（通过自组装和拆卸的主动运输）和微管的动态不稳定性，通过使用具有可以分离和研究的中间组装阶段的Holliday结异构化固有的驱动力;以及使用全面的单分子表征方法来可视化和控制DNA装配线的快速铣削和动态不稳定性。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。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马达蛋白运动的编程动态组装线（例如，动力蛋白或驱动蛋白）。