Mitigating Biological Signalling Cross-talk with Feedback Control

Biological signalling networks provide decision making and control capabilities for cells as they interact with changing physiological and environmental conditions. Studies of these signalling networks have revealed that they are greatly inter-dependent, which can make isolated analysis of their behaviour challenging. An accurate understanding of the inter-dependence of these systems will thus be of great utility to synthetic biologists as they attempt to engineer control systems within living cells. Cross-talk, which arises when the response of one signalling pathway can directly influence that of another, should either be considered explicitly when designing new signalling networks or controlled to ensure its effects are minimised. In this paper we consider a simple one-kinase two-phosphatase system and investigate potential control schemes that can reduce the impact of cross-talk upon its behaviour, for example by acting to selectively inhibit a kinase enzyme's affinity for one of its target substrates. We demonstrate that these schemes can be used to reduce the impact of crosstalk, and that a closed-loop control architecture provides better performance over a larger range of parameter values when compared to an open-loop equivalent.