A Synthetic Signaling Network Imitating the Action of Immune Cells in Response to Bacterial Metabolism

Abstract

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.

Co-transcriptional production of programmable RNA condensates and synthetic organelles

“…Among the many design features that can be straightforwardly controlled are nanostar valency, flexibility and arm-length, all known to predictably influence self-assembly in analogous DNA systems [21, 23, 28, 41, 67]. Control over condensatesize could be achieved by co-transcribing monovalent, surface passivating RNA constructs [68, 69]. Further RNA aptamers might be embedded to recruit molecular guests, including enzymes and metabolites, while ribozymes [70] could confer catalytic properties to the synthetic MLOs.…”

Lipid vesicle-based molecular robots

“…Molecular robots typically require encapsulation within a compartment, which acts as a boundary, separating the interior from the exterior environment. Various types of compartments have been employed to date, including lipid membranes, 21 hydrogels, 22 block co-polymers, 23 DNA droplets, 24 and coacervates, 25 each offering distinct advantages and limitations. Some researchers have explored the formation of hybrid chassis by combining different compartment types, leveraging the advantages associated with each constituent part.…”