Emergence of qualitative states in synthetic circuits driven by ultrasensitive growth feedback

Author summaryThe mutual inhibitory effect between synthetic gene circuits and cell growth produces growth feedback in the host-circuit system. Previous studies have demonstrated that the growth feedback could significantly impact the dynamics of the host-circuit system. However, the complexity of the growth feedback impact is not fully understood. Here, our data analysis displays ultrasensitive growth feedback between the cells and synthetic gene circuits under different growth conditions. To study the effect of ultrasensitive growth feedback on the host-circuit system, we develop a mathematical modeling framework. Our results reveal the emergence of qualitative states on the host-circuit system induced by ultrasensitive growth feedback. We found an emergence of bistability in a simple synthetic gene circuit with a constitutive promoter. Also, tristability could be seen in self-activation and toggle switch circuits. Our research uncovered the effect of ultrasensitive growth feedback in synthetic gene circuits and host interactions. Understanding the effects of ultrasensitive growth feedback could help scientists and engineers identify unexpected outcomes in gene circuits and formulate control strategies. The mutual interactions between the synthetic gene circuits and the host growth could cause unexpected outcomes in the dynamical behaviors of the circuits. However, how the steady states and the stabilities of the gene circuits are affected by host cell growth is not fully understood. Here, we developed a mathematical model for nonlinear growth feedback based on published experimental data. The model analysis predicts that growth feedback could significantly change the qualitative states of the system. Bistability could emerge in a circuit without positive feedback, and high-order multistability (three or more steady states) arises in the self-activation and toggle switch circuits. Our results provide insight into the potential effects of ultrasensitive growth feedback on the emergence of qualitative states in synthetic circuits and the corresponding underlying mechanism.

Automated summary

The study revealed the existence of ultrasensitive growth feedback between cells and synthetic gene circuits. A mathematical model was developed to analyze the effect of ultrasensitive growth feedback on the host-circuit system. Bistability and high-order multistability were observed in different types of circuits. Understanding the impact of ultrasensitive growth feedback could help predict unexpected outcomes in gene circuits and formulate control strategies.