Enhancing the speed of DNA walkers through soft confinement

Abstract

Over the past two decades, dynamic DNA origami structures have emerged as promising candidates for nanoscale signal and cargo transport. DNA walkers, programmable nanostructures that traverse tracks made of DNA, represent a key innovation in this field, enabling controlled and directional movement at the nanoscale. Despite relatively fast diffusion rates, the speed of DNA walkers remains constrained by the reaction-limited nature of strand exchange mechanisms, which depend both on the foothold-walker affinity and on the probability of the molecules being found close enough to bind. In this study, we explore how spatial confinement can expedite walker motion and evaluate two strategies to achieve this: the introduction of tailed DNA footholds, promoting pseudo-rotational dynamics, and the addition of walls along the DNA track, promoting pseudo-curvilinear dynamics. Using simulations and stochastic theories, we demonstrate that, by reducing the sampling of conformations far from the binding sites, tailed footholds provide the best speed enhancement, achieving a fourfold increase in speed. Trench-like confinement yields a more modest threefold increase, what, while significant, requires extensive structural modifications to the DNA track, limiting design flexibility and reducing cost-efficiency in comparison to the tailed footholds. The combination of tailed footholds and trench-like confinement turns the walker-foothold system bistable, with two distinct stable states separated by an energy barrier. By focusing on the properties of the DNA track, this study offers novel insights into leveraging soft structural motifs to optimize signal propagation rates, with implications for sensing, robotics and molecular computing in reaction-diffusion systems.