Versatile biomanufacturing through stimulus-responsive cell–material feedback

Small-scale production of biologics has great potential for enhancing the accessibility of biomanufacturing. By exploiting cell–material feedback, we have designed a concise platform to achieve versatile production, analysis and purification of diverse proteins and protein complexes. The core of our technology is a microbial swarmbot, which consists of a stimulus-sensitive polymeric microcapsule encapsulating engineered bacteria. By sensing the confinement, the bacteria undergo programmed partial lysis at a high local density. Conversely, the encapsulating material shrinks responding to the changing chemical environment caused by cell growth, squeezing out the protein products released by bacterial lysis. This platform is then integrated with downstream modules to enable quantification of enzymatic kinetics, purification of diverse proteins, quantitative control of protein interactions and assembly of functional protein complexes and multienzyme metabolic pathways. Our work demonstrates the use of the cell–material feedback to engineer a modular and flexible platform with sophisticated yet well-defined programmed functions. Encapsulation of engineered bacteria in environmentally responsive materials enables on-demand protein production coupled to downstream processes such as protein purification, on-chip enzyme kinetics and metabolic production of fatty acids.