‘Bottom-up fabrication’, which exploits the intrinsic properties of atoms and molecules to direct their self-organization, is widely used to make relatively simple nanostructures. A key goal for this approach is to create nanostructures of high complexity, matching that routinely achieved by ‘top-down’ methods. The self-assembly of DNA molecules provides an attractive route towards this goal. Here I describe a simple method for folding long, single-stranded DNA molecules into arbitrary two-dimensional shapes. The design for a desired shape is made by raster-filling the shape with a 7-kilobase single-stranded scaffold and by choosing over 200 short oligonucleotide ‘staple strands’ to hold the scaffold in place. Once synthesized and mixed, the staple and scaffold strands self-assemble in a single step. The resulting DNA structures are roughly 100 nm in diameter and approximate desired shapes such as squares, disks and five-pointed stars with a spatial resolution of 6 nm. Because each oligonucleotide can serve as a 6-nm pixel, the structures can be programmed to bear complex patterns such as words and images on their surfaces. Finally, individual DNA structures can be programmed to form larger assemblies, including extended periodic lattices and a hexamer of triangles (which constitutes a 30-megadalton molecular complex).
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I thank E. Winfree for discussions and providing a stimulating laboratory environment; B. Yurke for the term ‘nanobreadboard’; N. Papadakis, L. Adleman, J. Goto, R. Barish, R. Schulman, R. Hariadi, M. Cook and M. Diehl for discussions; B. Shaw for a gift of AFM tips; A. Schmidt for coordinating DNA synthesis; and K. Yong, J. Crouch and L. Hein for administrative support. This work was supported by National Science Foundation Career and Nano grants to E. Winfree as well as fellowships from the Beckman Foundation and Caltech Center for the Physics of Information.
The California Institute of Technology has filed a provisional patent on the method for design and creation of the folded DNA structures (scaffolded DNA origami) described in this paper. Paul W. K. Rothemund is named as the inventor on this patent.
Notes on the design process; helix bending and the inter-helix gap; models and sequences; experimental methods; control experiments; patterning with dumbbell hairpins; the combination of shapes into larger structures; secondary structure of the scaffold and staples; the robustness of the scaffolded approach; the cost of the scaffold versus staples; and additiona references. (PDF 6156 kb)
Full designs for all structures. Staple sequences are drawn out explicitly where they occur in the design. Because the designs are very large and the fonts are very small, this file will not print legibly. Instead of printing this file, open it in a PDF viewer and use the zoom feature to inspect the designs. (PDF 188 kb)
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Rothemund, P. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297–302 (2006). https://doi.org/10.1038/nature04586
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