Ultrasensitive Negative Feedback Control: A Natural Approach for the Design of Synthetic Controllers
Public Library of Science
Copyright: © 2016 Montefusco et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Many of the most important potential applications of Synthetic Biology will require the ability to design and implement high performance feedback control systems that can accurately regulate the dynamics of multiple molecular species within the cell. Here, we argue that the use of design strategies based on combining ultrasensitive response dynamics with negative feedback represents a natural approach to this problem that fully exploits the strongly nonlinear nature of cellular information processing. We propose that such feedback mechanisms can explain the adaptive responses observed in one of the most widely studied biomolecular feedback systems—the yeast osmoregulatory response network. Based on our analysis of such system, we identify strong links with a well-known branch of mathematical systems theory from the field of Control Engineering, known as Sliding Mode Control. These insights allow us to develop design guidelines that can inform the construction of feedback controllers for synthetic biological systems.
This work was funded by the UK Engineering and Physical Sciences Research Council (EPSRC), grant number EP/I017445/1.
This is the final version of the article. Available from Public Library of Science via the DOI in this record.
Vol. 11 (8), article e0161605