Broadening the Scope of DNA Origami Mechanical Design

Name: Yuchen Wang

Abstract:
DNA is a fundamental material with a central role in biology to store genetic information, yet it has also been used as the building block for structural nanotechnology. DNA origami is a technique for folding DNA strands into a target 2D or 3D structure with nanometer spatial resolution, which has greatly improved design complexity and applications such as nanofabrication, molecular computation, molecular machines, bioimaging, and drug delivery. Additionally, it provides a toolbox for designing artificial nanomachines with programmable abilities to generate mechanical motions, making these devices highly promising for achieving challenging nanorobotic tasks. Prior work from our laboratory and others have shown DNA origami provides a nanoscale platform that can leverage from macro-world inspiration, such as concepts from engineering machine design, control algorithms or artificial intelligence. Here, we focus on advancing the mechanical capabilities of DNA nanodevices, for example to enhance functions like force application. We achieve this by developing methods to modulate the free energy landscape of DNA nanodevices to enable control over mechanical and dynamic properties. We apply these nanomechanical design concepts to two different nanodevices: (Nanoscale DNA Force Spectrometer) nDFS and SteriDyn. nDFS is used as a novel biophysical assay for conducting force spectroscopy studies on biological samples such as chromatin sub-structures, while the SteriDyn is used as a proof-of-concept for achieving allosteric control and steric signal communication in dynamic DNA devices. Furthermore, we developed a machine-learning-based pipeline that greatly accelerates characterization of dynamic DNA devices through YOLOv5 and Resnet neural networks, overcoming one of the key bottlenecks of conformation analysis. Finally, we designed an education module for a mechanical classroom by reducing the overall experimental cost, increasing exposure to DNA nanotechnology for the public. These results demonstrate new advanced mechanical functions and establish tools and foundational principles to continue advancing the design and application of DNA nanomachines and nanorobots.

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Committee Members
Professor Carlos Castro
Professor Michael Poirier
Professor Ralf Bundschuh
Associate Professor Jonathan Song