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

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

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.