DNA Programmable Protocell Aggregation Behavior

Synthetic systems mimicking biological cells with simplified structures and functions are known as protocells. Various cell behaviors have been demonstrated with such model systems. Cell aggregation is an important function involved in cell viability, differentiation, and migration. Here, we propose a synthetic model system to study the cell interactions and signaling process in cell aggregation. We developed engineered lipid vesicles as a structural model for protocells with DNA strands attached on the surface. Two kinds of DNA-decorated vesicles were used in the experiments. Giant unilamellar vesicles (GUVs) were integrated with transmembrane channels made of DNA origami for recognizing and processing intercellular signals. Small unilamellar vesicles (SUVs) were modified with DNA strands responding to the DNA signals. Our experiments showed successful aggregation and dissociation between SUVs and GUVs upon introduction of proper DNA signals. We demonstrated that the DNA signals can be recognized by the GUVs and processed by the encapsulated enzymes to perform programmed aggregation behavior. The DNA programmable protocells have the potential as model systems for studying intricate cell signaling and cell-to-cell communication.