Synchrony and pattern formation of coupled genetic oscillators on a chip of artificial cells

Abstract

Understanding how biochemical networks lead to large-scale nonequilibrium self-organization and pattern formation in life is a major challenge, with important implications for the design of programmable synthetic systems. Here, we assembled cell-free genetic oscillators in a spatially distributed system of on-chip DNA compartments as artificial cells, and measured reaction–diffusion dynamics at the single-cell level up to the multicell scale. Using a cell-free gene network we programmed molecular interactions that control the frequency of oscillations, population variability, and dynamical stability. We observed frequency entrainment, synchronized oscillatory reactions and pattern formation in space, as manifestation of collective behavior. The transition to synchrony occurs as the local coupling between compartments strengthens. Spatiotemporal oscillations are induced either by a concentration gradient of a diffusible signal, or by spontaneous symmetry breaking close to a transition from oscillatory to nonoscillatory dynamics. This work offers design principles for programmable biochemical reactions with potential applications to autonomous sensing, distributed computing, and biomedical diagnostics.