DNA nanotechnology and Toehold Mediated Strand Displacement (TMSD) offer the possibility of building systems that display complex algorithmic behaviours. However, up to the present point most systems based in this technology act as one-shot systems that relax into equilibrium when they operate and lose any chance of responsiveness and adaptation to changing environmental outputs.
This situation is starkly opposed to how living systems react to changes in their environment and implement finely-tuned responses. Cells perform this feat via biochemical transduction networks, which have previously been described as distributed computational systems operating out of thermodynamic equilibrium. While transduction networks are highly complex, their fundamental building motif is well known: the push-pull network. In this motif, a substrate is switched between two states via two fuel-consuming catalysts. This out-of-equilibrium operation allows push-pull systems to propagate information robustly in signal-transduction cascades presenting while complex dynamics.
Understanding the main operational constraints of push-pull systems is a fundamental question in systems biology and a requirement for their proper use in synthetic biology. Moreover, building DNA-based analogues of push-pull systems would allow us to explore these fundamental questions and provides an ideal engineering platform for implementing non-equilibrium information processing systems in biological and nanotechnology contexts.
While emulating the behaviour of transduction network in TMSD systems is possible in principle, there are several performance issues that hinder this possibility. In order to overcome these limitations, we propose the Active Circuits of Duplex Catalysts (ACDC) Framework to meet this challenge. In ACDC, all species are DNA duplexes that interact directly via four-way strand exchange. The present thesis demonstrates that the ACDC Framework can successfully implement all the prerequisite to build extended catalytic reaction networks. Additionally, we discuss functional and formal limitations of the Framework as well as the role of thermodynamic drives in overcoming them.