Self-Assembly Processes in DNA Nanostructures

Jacob Majikes,1 Daniel Schiffels1,2, Samuel P. Forry, Michael Zwolak,1 Veronika Szalai,1 J. Alexander Liddle1
1Microsystems and Nanotechnology Division, Physical Measurement Laboratory, NIST, 100 Bureau Drive, Gaithersburg, MD 20899
2 Maryland NanoCenter, University of Maryland, College Park, MD 20742
[email protected]

The Microsystems and Nanotechnology Division at NIST develops and applies top-down and bottom-up nanofabrication methods to create highly functional structures. In this talk I will give a brief overview of some of the division’s activities in nanophotonics, plasmonics, and NEMS, before describing my own research in DNA-based self-assembly.
Biology uses self-assembly processes to form structures of astonishing complexity and functionality. Synthetically, however, it remains challenging to replicate the properties of biological constructs. Self-assembly mediated by DNA is a powerful method with which to build multi-functional, molecularly-addressable nanostructures of arbitrary shape. While recent developments in DNA nanostructure fabrication have expanded the design space, fabrication based on DNA alone can suffer from low yields and is hampered by the need to strike a balance between size and mechanical rigidity. Typical assembly protocols, employing large numbers of discrete components, offer little control over the assembly pathway, limiting structure size, complexity, and yield.
We are working to understand the details of the assembly pathway in DNA origami, and to develop strategies to mitigate the formation of defects.
DNA origami assembly begins with a pair of hybridization events that enable a short staple oligonucleotide to bring together distant regions of a long scaffold strand. The entropic costs associated with making this fold play a key role, both at thermal equilibrium and when kinetics dominate. We use fluorescence melting curves to measure the effect of scaffold topology on the thermodynamics of this first assembly step.
The number of defects in a self-assembling system can be reduced by minimizing the number of discrete components, and thus the number of pathways leading to improperly assembled structures. We minimize the amount of information encoded in a DNA template to direct a two-stage, hierarchical self-assembly process, to create otherwise inaccessible structures. Expanding the self-assembly toolbox by blending sequence-specific and structure-specific elements, enables us to make micrometer-scale, rigid, molecularly-addressable structures.
By gaining a deeper understanding of self-assembling systems, we hope to enable synthetic methods to approach the exquisite complexity and functionality of natural ones.

J. Alexander Liddle received his B.A. and D. Phil. degrees in Materials Science from the University of Oxford. After his appointment in 1990 as a postdoctoral fellow at Bell Laboratories, he spent the next eleven years there, where his primary efforts were directed towards the research, development, and eventual commercialization of a novel electron-beam lithography technology. He subsequently became the leader of an optical telecommunications micro-electromechanical systems (MEMS) group when Agere Systems spun-off from Lucent Technologies. He spent the next three years as the head of the Lawrence Berkeley National Laboratory nanofabrication group in the Center for X-ray optics. During that time, he worked as part of the team standing up the Molecular Foundry nanoscience user facility before becoming lead scientist of the nanofabrication group. His research at LBNL ranged from investigations of solid-state devices for quantum computation to guided self-assembly for integrated circuit fabrication, with an emphasis on the science of nanofabrication. In 2006 he moved to NIST, where he is now a Senior Scientist and leader of the Nanofabrication Research Group in the Center for Nanoscale Science and Technology. His group works in a variety of areas, ranging from nanophotonics to in situ electron microscopy. His personal research focus is on nanofabrication and self-assembly for nanomanufacturing. He has published over 250 papers, and holds 16 US patents, in areas ranging from electron-beam lithography to DNA-controlled nanoparticle assembly. He is a fellow of the APS and the Washington Academy of Sciences, and a member of the AVS and MRS. He has served on numerous advisory and program evaluation committees, including those for NSF, DOE, and the Semiconductor Research Corporation.

Interdisciplinarity, team science, applied science, NIST value of scientific rigor leading to trustworthy science.