The assembly of artificial cells capable of executing synthetic DNA programs has been an important goal for basic research and biotechnology. We assembled two-dimensional DNA compartments fabricated in silicon as artificial cells capable of metabolism, programmable protein synthesis, and communication. Metabolism is maintained by continuous diffusion of nutrients and products through a thin capillary, connecting protein synthesis in the DNA compartment with the environment. We programmed protein expression cycles, autoregulated protein levels, and a signaling expression gradient, equivalent to a morphogen, in an array of interconnected compartments at the scale of an embryo. Gene expression in the DNA compartment reveals a rich, dynamic system that is controlled by geometry, offering a means for studying biological networks outside a living cell.

SignificanceSynchrony, entrainment, and pattern formation are nonlinear modes of communication and collective behavior in living systems across scales. We aim to understand these complex processes by building them bottom-up in a minimal environment to unravel basic rules governing their behavior. However, it has so far been challenging to emulate spatially distributed coupled gene expression cellular reactions. We show a microfluidic device of a confined coupled system of DNA compartments programmed with nonlinear genetic oscillator and diffusion-based communication. This approach provides unique control of experimental parameters, which reveals a rich phenomenology of cell-free gene expression patterns in space and time.

Living systems employ front propagation and spatiotemporal patterns encoded in biochemical reactions for communication, self-organization and computation 1-4 . Emulating such dynamics in minimal systems is important for understanding physical principles in living cells [5][6][7][8] and in vitro 9-14 . Here, we report a one-dimensional array of DNA compartments in a silicon chip as a coupled system of artificial cells, o ering the means to implement reaction-di usion dynamics by integrated genetic circuits and chip geometry. Using a bistable circuit we programmed a front of protein synthesis propagating in the array as a cascade of signal amplification and short-range di usion. The front velocity is maximal at a saddle-node bifurcation from a bistable regime with travelling fronts to a monostable regime that is spatially homogeneous. Near the bifurcation the system exhibits large variability between compartments, providing a possible mechanism for population diversity. This demonstrates that on-chip integrated gene circuits are dynamical systems driving spatiotemporal patterns, cellular variability and symmetry breaking.Sharp travelling fronts are prevalent in nature and emerge when nonlinear and dispersive effects combine, for example solitary waves in nonlinear optics, fluid convection, and chemical reactions 15 . Biological multicellular systems use travelling fronts of molecular signals as a means for computation and communication over long distances when signalling by diffusion is inefficient. In these systems, cells can be described as autocatalytic units that amplify and transmit signals beyond a threshold. Because signals dissipate in the medium over short distances, long-range information transmission is achieved by consecutive local cell-cell interactions. Signal propagation has been measured over orders of magnitudes in a variety of biological processes, ranging from fast action potentials in neuron networks with typical velocities 16 of v ≈ 10 7 mm h −1 , to slow gene expression fronts in development 3 with v ≈ 0.1 mm h −1 . Although some systems have a linearly unstable initial state, and thus can be treated as Fisher waves 17 , the majority of biological examples require more complex models, including the cable equation and Hodgkin-Huxley model 18 . These systems raise questions concerning the selected speed, bifurcations, fluctuations and stability in parameter space 15 , which are challenging to study in a living organism.Front propagation has been extensively studied in chemical reactions 16,19 and more recently in reconstituted biological systems, including the bacterial cell division network 10 , the Xenopus laevis cell cycle 11 , and RNA (ref. 20) and DNA (ref. 14) catalytic reactions. In the past decade cell-free transcription-translation reactions have been used to advance the design of programmable artificial gene systems, including bulk solution 21 , gels 9 , membrane vesicles 22 , water-in-oil drops 23 , microfluidic devices 24 and on-chip DNA compartments 13 . So far, however, a synthet...

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