Threshold‐Gated DNA Nanocages Enable Programmable Quorum‐Like Sensing in Vesicle Communities

ABSTRACT Microorganisms often form multimodal communities through spatial organization and coordinate collective responses via quorum sensing, which is driven by threshold accumulation of autoinducers. While artificial communities are attractive for sensing and smart materials, current systems often lack interfacial gating mechanisms with threshold‐switchable properties, making it difficult to precisely encode density‐dependent, threshold‐triggered responses associated with quorum‐like sensing. Here, we employed naturally secreted extracellular vesicles as a model community system and developed an encapsulation strategy using programmable, threshold‐gated DNA nanocages. This surface‐encapsulation strategy preserves individual integrity during community assembly by preventing membrane fusion. It also enables the programmed construction of dual‐component multimodal communities, including homogeneous clusters, core‐shell structures, and heterogeneous clusters, using sequence‐programmable DNA nanocages. By introducing pH gating and using H ⁺ generated by a GOX‐CAT positive‐feedback circuit as the autoinducer, we achieved density‐dependent signal accumulation and threshold‐triggered reversible structural switching, thereby exhibiting key operational features of quorum‐like sensing in vesicle‐based communities. This platform provides a general model for studying community organization and cooperative behaviors, with potential applications in biomimetic sensing, programmable smart materials, and stimulus‐responsive delivery systems.