Artificial Cells with Controllable Central Dogma Activities as a Tool for Understanding Complex Biological Events

In nature, intracellular micro-compartments have evolved to allow the simultaneous execution of tightly regulated complex processes within a controlled environment. This architecture serves as the blueprint for the construction of a wide array of artificial cells. However, such systems are limited in their ability to confine and sequentially control multiple central dogma activities. Here, we designed and fabricated an artificial cell-on-a-chip comprising hierarchical compartments allowing the processing and transport of products from transcription, translation and post-translational modifications through connecting microfluidic channels. This platform generates a tightly controlled system, yielding directly a purified proteoform of choice. Using this platform, we were able to generate, in a single device, the full ubiquitinated form of the Parkinson’s disease-associated α-synuclein starting from DNA. By bringing together all central dogma activities in a single controllable platform, this approach will open up new possibilities for the synthesis of complex targets, will allow to decipher diverse molecular mechanisms in health and disease and to engineer protein-based materials and pharmaceutical agents.