Biological and Soft Systems, Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge, CB3 0HE, UK.
Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
Adv Mater. 2023 Aug;35(33):e2301562. doi: 10.1002/adma.202301562. Epub 2023 Jul 9.
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.
基于最新发展的从下到上的合成生物学，可以在类似人工细胞的设备中复制许多基本的生物学功能。然而，要模拟更复杂的行为，人工细胞需要以协同和协调的方式执行许多这些功能，而这仍然难以实现。在这里，考虑了一种复杂的生物反应，即中性粒细胞免疫细胞通过网质细胞形成过程捕获和失活病原体。设计了由两个合成剂组成的联合体——响应性基于 DNA 的颗粒和载有抗生素的脂质体——当被细菌代谢触发时，其协调作用模拟了所寻求的免疫样反应。人工网质细胞样反应源自活的和合成的试剂之间的一系列相互关联的传感和通信途径，并转化为物理和化学的抗菌作用，即细菌固定化和暴露于抗生素。结果表明，如何用相对较少的合成分子成分来规定先进的类生命反应，并为基于人工细胞的抗菌解决方案概述了一种新策略。
