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.
From ligand–receptor binding to DNA hybridization, molecular recognition plays a central role in biology. Over the past several decades, chemists have successfully reproduced the exquisite specificity of biomolecular interactions. However, engineering multiple specific interactions in synthetic systems remains difficult. DNA retains its position as the best medium with which to create orthogonal, isoenergetic interactions, based on the complementarity of Watson–Crick binding. Here we show that DNA can be used to create diverse bonds using an entirely different principle: the geometric arrangement of blunt-end stacking interactions. We show that both binary codes and shape complementarity can serve as a basis for such stacking bonds, and explore their specificity, thermodynamics and binding rules. Orthogonal stacking bonds were used to connect five distinct DNA origami. This work, which demonstrates how a single attractive interaction can be developed to create diverse bonds, may guide strategies for molecular recognition in systems beyond DNA nanostructures.