Programmable On-Chip DNA Compartments as Artificial Cells

Toward an “artificial cell” on a chip Cell-free systems that reconstitute biochemical pathways have been critical for unraveling the inner workings of the cell. Karzbrun et al. created a highly miniaturized cell-free system on a silicon chip. A series of tiny linked compartments were fabricated on the chip, in which DNA-driven reactions occurred, with materials flowing into and diffusing between the compartments. The system recreated oscillating protein expression patterns and protein gradients, and provides a stepping stone to creating “artificial cells” on a chip. Science, this issue p. 829 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. DNA-driven biochemical reactions on a fabricated silicon chip recreate protein gradients and oscillations. DNA-driven biochemical reactions on a fabricated silicon chip recreate protein gradients and oscillations.