Dynamic control in a coordinated multi-cellular maze solving system

Control system theory provides convenient tools and concepts for describing and analyzing complex cell functions. In this paper we demonstrate the use of control theory to forward-engineer a complex synthetic gene network constructed from several modular components. Specifically, we present the design and simulation of a synthetic multi-cellular maze-solving system. Here, bacterial cells are programmed to use artificial cell-to-cell communication and regulatory feedback in order to illuminate the correct path in a user-defined maze of cells arranged on a surface. Simulations were used to analyze the system's spatiotemporal dynamics and sensitivity to various kinetic parameters. Experiments with Escherichia coli were carried out to characterize the diffusion properties of artificial cell-to-cell communication based on bacterial quorum sensing systems. The rational design process and simulation tools employed in this study provide an example for future engineering of complex synthetic gene networks comprising multiple control system motifs.