Responsive DNA artificial cells for contact and behavior regulation of mammalian cells

Artificial cells have emerged as synthetic entities designed to mimic the functionalities of natural cells, but their interactive ability with mammalian cells remains challenging. Herein, we develop a generalizable and modular strategy to engineer DNA-empowered stimulable artificial cells designated to regulate mammalian cells (STARM) via synthetic contact-dependent communication. Constructed through temperature-controlled DNA self-assembly involving liquid-liquid phase separation (LLPS), STARMs feature organized all-DNA cytoplasm-mimic and membrane-mimic compartments. These compartments can integrate functional nucleic acid (FNA) modules and light-responsive gold nanorods (AuNRs) to establish a programmable sense-and-respond mechanism to specific stimuli, such as light or ions, orchestrating diverse biological functions, including tissue formation and cellular signaling. By combining two designer STARMs into a dual-channel system, we achieve orthogonally regulated cellular signaling in multicellular communities. Ultimately, the in vivo therapeutic efficacy of STARM in light-guided muscle regeneration in living animals demonstrates the promising potential of smart artificial cells in regenerative medicine.