Quantifying crosstalk in biochemical systems

Recent work has introduced biocircuit architectures that exhibit robust oscillatory behavior in organisms ranging from cyanobacteria to mammals. Complementary research in synthetic biology has introduced oscillators in vivo and in vitro suggesting that robust oscillation can be recapitulated using a small number of biochemical components. In this work, we introduce signaling crosstalk in biocircuits as a consequence of enzyme-mediated biochemical reactions. As a motivating example, we consider an in vitro oscillator with two types of crosstalk: crosstalk in production and degradation of RNA signals. We then propose a framework for quantifying crosstalk and use it to derive several dynamical constraints and suggest design techniques for ameliorating crosstalk in vitro biochemical systems. We demonstrate that the effects of crosstalk can be attenuated through the effective tuning of two key parameters in order to recover desired system dynamics. As an example, we show that by changing the balance between production and degradation crosstalk, we can tune a system to be stable or exhibit oscillatory behavior.