Singh Seminar Series: Unlocking the Magic of DNA Origami

Cooperativity in self-assembly – unlocking the magic of DNA origami

Speaker: J. Alexander Liddle, National Institute of Standards and Technology

Since its invention in 2006, DNA origami has been the leading method for creating nucleic acid nanostructures. Despite widespread adoption, the mechanisms responsible for its remarkably robust performance have remained elusive. This is due to the complexity of the assembly process, which involves about 200 oligomers, each with multiple binding domains, hybridizing with a scaffold strand in about 600 reactions. This complexity creates three interconnected problems that must be solved. First, the sources of cooperativity must be identified, second, we must devise quantitative metrics to accurately capture those sources, and third, we must find ways to deconvolve their effects.

Fortunately, the solution lies in another complex aspect of origami – its design. Even for a simple origami structure, such as a rectangle of defined size, there are an almost infinite number of choices to made in terms of the combination of oligomer length, location, binding domain size and distribution, sequence, etc., leading to different distributions of cooperative effects, that affect the assembly defectivity, thus providing some insight into this balance. We therefore use 2D design variations to probe cooperative effects. Our results have led us to a set of quantitative metrics connecting design to defectivity that are both physically intuitive and highly predictive. We have thus provided the first comprehensive quantitative insight into this complex self-assembly process.

About the Speaker

J. Alexander Liddle is the Chief of the Microsystems and Nanotechnology Division at NIST. He holds a D.Phil. and B.A. in Materials Science from the University of Oxford. His division’s research runs the gamut from quantum nanophotonics to biology. His personal research focus is on nanofabrication and self-assembly for nanomanufacturing. He has published over 275 papers, in areas ranging from electron-beam lithography to DNA-controlled nanoparticle assembly to super-resolution optical microscopy. He is a fellow of the American Physical Society and the Washington Academy of Sciences.

Host or Publisher Gerald Lopez, PhD