A Synthetic Signaling Network Imitating the Action of Immune Cells in Response to Bacterial Metabolism
Bottom?up synthetic biology aims to replicate useful biological functions, but mimicking complex behaviors such as immunity remains elusive. In this work, a consortium of DNA particles and liposomes is shown to detect bacteria, trap them, and expose them to antibiotics, imitating a response of the immune system. These results demonstrate the bottom?up design of advanced life?like responses and outline new antimicrobial strategies. State?of?the?art bottom?up synthetic biology allows to replicate many basic biological functions in artificial?cell?like devices. To mimic more complex behaviors, however, artificial cells would need to perform many of these functions in a synergistic and coordinated fashion, which remains elusive. Here, a sophisticated biological response is considered, namely the capture and deactivation of pathogens by neutrophil immune cells, through the process of netosis. A consortium consisting of two synthetic agents is designed—responsive DNA?based particles and antibiotic?loaded lipid vesicles—whose coordinated action mimics the sought immune?like response when triggered by bacterial metabolism. The artificial netosis?like response emerges from a series of interlinked sensing and communication pathways between the live and synthetic agents, and translates into both physical and chemical antimicrobial actions, namely bacteria immobilization and exposure to antibiotics. The results demonstrate how advanced life?like responses can be prescribed with a relatively small number of synthetic molecular components, and outlines a new strategy for artificial?cell?based antimicrobial solutions.