Scientists from Duke University have recently demonstrated a new method for assembling large, low-cost DNA nanostructures, in part by reusing the “sticky-ends,” the broken DNA strands used to connect the nanostructures. In their hierarchical self-assembly method, the scientists have demonstrated one of the largest programmable synthetic nanostructures ever synthesized.
The hierarchical approach to building nanostructures from DNA, beginning with nine oligonucleotides and resulting in an 8 x 8 grid. Credit: Constantin Pistol, et al.
At a molecular weight of 8960 kD, the 64-motif structure is one of the largest programmable synthetic nanostructures ever synthesized. The scientists also predict that this method can be scaled even further before reaching a limit imposed when the generic interactions begin to dominate the process. However, studies in periodic DNA crystal formation suggest that the scale limit is nearly macroscopic.
The first type, the “generic” sticky-end, binds with only one helix instead of the normal two. This binding provides a relatively unstable interaction, which makes it easier to individually program two adjacent grids later on. The second type, the “specific” sticky-end, provides a stronger interaction and can control the weak interactions between the generic sticky-ends.
In one fabrication method, the scientists bound together two 4 x 4 grids, using two generic sticky-ends and one specific sticky-end (the fourth grid arm was left open for identification purposes). The scientists found that the single specific sticky-end could dominate the entire connection, providing a scalable assembly method.
In the second method, Pistol and Dwyer used all specific sticky-ends to connect two 4 x 4 grids. They found that, after the grids were connected, the sticky-ends could be reused in other connections. In this method, the scientists assembled four 4 x 4 grids to produce a 64-motif structure.
In analyzing their structures for defects, Pistol and Dwyer found that missing motifs were common, requiring defect-tolerant designs in future large-scale assemblies. “One of the benefits of DNA nanostructures for computers is device density,” Dwyer said. “The grid has a pitch of 20nm, and this is about half of the smallest device feature in Intel's latest lithography process. The other benefit is manufacturing scale. Each experiment created a vast number of structures (~1012 or more) and this holds the promise of more complex and higher performance computers in the future.”