Abstract
Growth-mediated feedback between synthetic gene circuits and host organisms leads to various emerged behaviors, including innate growth bistability and increased ultrasensitivity. However, the adverse impact of growth feedback on gene circuits remains unexplored. Here, we found that the effects of growth feedback on the functional perturbations of gene circuits depend on the network topology. Specifically, the memory of a self-activation circuit is lost due to the fast growth of host cells. Decoupling of growth feedback reveals its hysteresis property in a broad range. Interestingly, the toggle switch circuit is more refractory to the growth feedback. The underlying principle is demonstrated by modeling the interplay between microbial growth and the gene circuit. Our results reveal a topology-dependent mechanism underlying the functional perturbation of gene circuits by growth-mediated feedback.