Artificial morphogen-mediated differentiation in synthetic protocells

The design and assembly of artificial protocell consortia displaying dynamical behaviours and systems-based properties are emerging challenges in bottom-up synthetic biology. Cellular processes such as morphogenesis and differentiation rely in part on reaction-diffusion gradients, and the ability to mimic rudimentary aspects of these non-equilibrium processes in communities of artificial cells could provide a step to life-like systems capable of complex spatiotemporal transformations. Here we expose acoustically formed arrays of initially identical coacervate micro-droplets to uni-directional or counter-directional reaction-diffusion gradients of artificial morphogens to induce morphological differentiation and spatial patterning in single populations of model protocells. Dynamic reconfiguration of the droplets in the morphogen gradients produces a diversity of membrane-bounded vesicles that are spontaneously segregated into multimodal populations with differentiated enzyme activities. Our results highlight the opportunities for constructing protocell arrays with graded structure and functionality and provide a step towards the development of artificial cell platforms capable of multiple operations.