Error Correction for DNA Self-Assembly: Preventing Facet Nucleation

Abstract. Algorithmic self-assembly has been proposed as a mechanism for bottom-up construction of nanostructures and autonomous DNA computation. For these applications, we are often interested in assembling large systems with great precision. However, several effects present in real systems result in errors with respect the the abstract Tile Assembly Model used for most theoretical studies. Hence the high error rate is becoming a key issue for algorithmic self-assembly. Several error correction mechanisms have been proposed for the self-assembly of DNA tiles [7, 4, 3, 1]. The “snaked proofreading” scheme of Chen and Goel [1], which builds on the simpler proofreading scheme of Winfree and Bekbolatov [7], provides a means to prevent undesired nucleation on facets of a growing crystal. This allowed for the first provable results that arbitrarily low error rates can be achieved with little cost (under some mild assumptions). Prior to this work, none of these schemes have been experimentally demonstrated. Here, we have implemented a twoby-two snaked proofreading system, and, for comparison, a two-by-two original proofreading system. As shown in Figure 1, the snaked system is a two-by-two block composed of a double tile and two single tiles which have an inert edge between them. To create long facets (the worst case situation for error control), we use the zig-zag tile set [6] implemented as DNA tiles [5] that self-assemble into long ribbons. One facet of the ribbon has sticky ends matching with side CD, and the other facet has sticky ends matching with side AB. Each snaked proofreading tile has at most one sticky end that can bind to either facet. Hence, according to the abstract Tile Assembly Model with attachment threshold τ = 2, no tiles are supposed to be attached to either facet; any such attachment can be viewed as an error. In the more realistic kinetic Tile Assembly Model, the snaked proofreading block reduces errors on the CD facet but has no error correction along the AB facet [1]. The original proofreading block has no error correction along either facet. In our experiments, we separately preform the zig-zag ribbons and each proofreading tile, then mix them at room temperature. At this low temperature, nucleation errors do happen on both sides of the zig-zag ribbon (Figure 1(d)). But side AB (which does not have error correction) has more snaked proofreading tiles attached than side CD (which does). An examination of a total length of 50 microns of zig-zag ribbon revealed 670 tiles attached on the CD side and 2714 tiles attached on the AB side, indicating a four-fold improvement in facet nucleation error rates under these conditions. (The original proofreading tiles attach equally to both sides, within experimental error.) This demonstrates that the basic principle of the snaked proofreading system is sound. It remains to be determined how the rates depend upon physical conditions and whether they can be improved by changing tile concentrations, annealing conditions, or other factors.