UBC Faculty Research and Publications

A coupled reconfiguration mechanism that enables powerful, pseudoknot-robust DNA strand displacement devices with 2-stranded inputs Johnson, Hope Amber; Condon, Anne

Abstract

DNA strand displacement, a collective name for certain behaviors of short strands of DNA, has been used to build many interesting molecular devices over the past few decades. Among those devices are general implementation schemes for Chemical Reaction Networks, suggesting a place in an abstraction hierarchy for complex molecular programming. However, the possibilities of DNA strand displacement are far from fully explored. On a theoretical level, most DNA strand displacement systems are built out of a few simple motifs, with the space of possible motifs otherwise unexplored. On a practical level, the desire for general, large-scale DNA strand displacement systems is not fulfilled. Those systems that are scalable are not general, and those that are general don’t scale up well. We have recently been exploring the space of possibilities for DNA strand displacement systems where all input complexes are made out of at most 2 strands of DNA. As a test case, we’ve had an open question of whether such systems can implement general Chemical Reaction Networks, in a way that has a certain set of other desirable properties—reversible, systematic, O(1) toeholds, bimolecular reactions, and correct according to CRN bisimulation—that the state-of-the-art implementations with more than 2-stranded inputs have. Until now we’ve had a few results that have all but one of those desirable properties, including one based on a novel mechanism we called coupled reconfiguration, but that depended on the physically questionable assumption that pseudoknots cannot occur. We wondered whether the same type of mechanism could be done in a pseudoknot-robust way. In this work we show that in fact, coupled reconfiguration can be done in a pseudoknot-robust way, and this mechanism can implement general Chemical Reaction Networks with all inputs being single strands of DNA. Going further, the same motifs used in this mechanism can implement stacks and surface-based bimolecular reactions. Those have been previously studied as part of polymer extensions of the Chemical Reaction Network model, and on an abstract model level, the resulting extensions are Turing-complete in ways the base Chemical Reaction Network model is not. Our mechanisms are significantly different from previously tested DNA strand displacement systems, which raises questions about their ability to be implemented experimentally, but we have some reasons to believe the challenges are solvable. So we present the pseudoknot-robust coupled reconfiguration mechanism and its use for general Chemical Reaction Network implementations; we present the extensions of the mechanism to stack and surface reactions; and we discuss the possible obstacles and solutions to experimental implementation, as well as the theoretical implications of this mechanism.