Abstract

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.

Highlights

  • An emerging design framework that uses abstract chemical reaction networks (CRNs) in the implementation of enzymefree, entropy driven DNA reactions has recently attracted much attention in the Synthetic Biology community following a number of successful studies [1]-[3]

  • The paper is organised as follows: Section II describes the abstract chemical reactions used in the design of the various control systems considered, while in Section III, we analyse the performance and robustness properties of the PI and SC feedback controllers when implemented in closedloop with a second order nonlinear biomolecular process

  • The PI controller is made up of three submodules: an integrator, a proportional gain and a summation junction. Together these sub-modules require a total of 15 abstract chemical reactions to implement, as follows: [Integrator:] e± −K→I e± + n± and n+ + n− −→η 0/, where KI is the integral gain of the PI controller and η is the annihilation rate

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Summary

INTRODUCTION

An emerging design framework that uses abstract chemical reaction networks (CRNs) in the implementation of enzymefree, entropy driven DNA reactions has recently attracted much attention in the Synthetic Biology community following a number of successful studies [1]-[3]. Examples of complex biomolecular circuits successfully designed and implemented through this approach include predator-prey dynamics [6], oscillators [7], and both linear and nonlinear feedback controllers [3], [8], [9]. We show how such a signalling-cycle (SC) controller can reproduce the input-output signal mapping of a classical PI controller, while requiring smaller numbers of abstract chemical reactions to implement. The paper is organised as follows: Section II describes the abstract chemical reactions used in the design of the various control systems considered, while, we analyse the performance and robustness properties of the PI and SC feedback controllers when implemented in closedloop with a second order nonlinear biomolecular process.

PI controller
SC controller
RESULTS AND DISCUSSIONS
CONCLUSIONS
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