Biologically inspired design of feedback control systems implemented using DNA strand displacement reactions.

The use of abstract chemical reaction networks (CRNs) as a modelling and design framework for the implementation of computing and control circuits using enzyme-free, entropy driven DNA strand displacement (DSD) reactions is starting to garner widespread attention in the area of synthetic biology. Previous work in this area has demonstrated the theoretical plausibility of using this approach to design biomolecular feedback control systems based on classical proportional-integral (PI) controllers, which may be constructed from CRNs implementing gain, summation and integrator operators. Here, we propose an alternative design approach that utilises the abstract chemical reactions involved in cellular signalling cycles to implement a biomolecular controller - termed a signalling-cycle (SC) controller. We compare the performance of the PI and SC controllers in closed-loop with a nonlinear second-order chemical process. Our results show that the SC controller outperforms the PI controller in terms of both performance and robustness, and also requires fewer abstract chemical reactions to implement, highlighting its potential usefulness in the construction of biomolecular control circuits.