Localized Cascade DNA Hybridization Chain Reactions of DNA Hairpins on a DNA Track

Theoretical models of localized DNA reactions on platforms indicate potential benefits to conventional DNA hybridization reactions. Recently locality has been proposed as a novel approach to speed up DNA hybridization reactions as well as to minimize incorrect binding among DNA sequences. Here we experimentally report evidence for a 169-fold speedup of localized DNA hybridization chain reactions in the system consisting of six DNA hairpin gates bound to a DNA track. Introduction DNA hybridization reactions have been wellstudied in the past decade and widely used to perform complex state changes and computation in DNA-based molecular computing.1–6 In most systems where DNA hybridization reactions are used for molecular computing, the reactants need to exist in low concentration (in the nano molar range) to avoid unwanted spurious bimolecular interactions. Hence diffusion of certain low concentration reactants generally plays an important factor in determination of the overall time for executing a computation. In addition, unintended crosstalk can still result in incorrect binding among DNA sequences. The above challenges have been reported in earlier studies.7 One feasible method to overcome those challenges is to tether DNA reac∗To whom correspondence should be addressed tions onto nanostructures,8 allowing for the hybridization reactions to occur locally. Recently there have been a few attempts at tethering DNA hybridization reactions on DNA nanostructures.9,10 For example, Kopperger et al. studied the diffusion transport of DNA cargo strands bound to a DNA origami rectangle;11 Teichmann et al. studied the effect of colocalization on the performance of DNA strand displacement reactions;12 Elezgaray et al. studied the performance of DNA amplification circuits through exploiting the effect of colocalization.13 These studies bound DNA gates to DNA platforms (i.e. DNA origami rectangles) and provided some evidence that locality (tethering DNA reactions to DNA platforms) can provide faster reaction rates. In addition to speeding up reactions, locality can be exploited to limit unintended crosstalk that can result in incorrect binding among DNA sequences. There are a few considerations in order to optimize the effect of locality on hybridization reactions. The distances between gates needs to be designed within the optimal range for the gates to interact with each other; too short a distance results in high leaks while a long distance results in losing unbound complimentary strands to the bulk solution.11 When the cascade reaction gates are bound to DNA platforms, the distances between those gates have to be optimal in order to prevent the intermediate strands from floating away to the bulk solution, resulting in signal loss. A feasible approach to prevent losing unbound strands to the bulk solution is to con-