Geometry of DNA nanostructures used to program molecular recognition

The wide assortment of nanostructures and nanomachines made possible by structural DNA nanotechnology are all based upon the molecular recognition code of the familiar DNA double helix. Initially this code was exploited to build atomically precise structures on the order of 20 nmm in size. Since the publication of the DNA origami technique by Paul W. K. Rothemund in 2006 it has been possible to fold a long single strand of DNA with the help of numerous short DNA ‘staples’ into larger and more complex two-dimensional and three-dimensional nanostructures on the order of 100 nm in size. In a recent publication [abstract], Rothemund and Sungwook Woo use a different type of molecular coding derived from DNA—blunt-end stacking interactions at the ends of DNA helices—to create molecular shape complementarity on a larger scale.

Rothemund’s earlier work making rectangular DNA tiles using DNA origami had revealed that the rectangles tended to form chains due to the blunt-end stacking interactions of the helix ends exposed at the edges of the tiles. In their current work Woo and Rothemund tested methods of making these blunt-end interactions specific so that multiple origami tiles could be assembled in a programmed fashion to make well-defined nanostructures. Through matching patterns of projecting and recessed ends at the edges of tiles, discrete segments could be made to assemble in a particular order to form larger structures approaching micrometer scale. The stacking interactions are weaker than base pairing interactions but permit building loser structures on a ten-times-larger scale. The researchers speculate that it might be possible to design larger nanomachines in which parts can be programmed to both self-assemble and slide freely past each other in a programmed way.

The Caltech DNA computation group has made three PDFs available on their web site describing the research in detail: the full text of the Nature Chemistry research paper “Programmable molecular recognition based on the geometry of DNA nanostructures“, a Nature Chemistry commentary by Andrew J. Turberfield, and a report on the work by Michael Eisenstein published in Nature Methods.

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