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

Miao Wang, Hexin Nan, Meixia Wang, Sihui Yang, Lin Liu, Hong-Hui Wang () and Zhou Nie ()
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Miao Wang: Hunan University
Hexin Nan: Hunan University
Meixia Wang: Hunan University
Sihui Yang: Hunan University
Lin Liu: Hunan University
Hong-Hui Wang: Hunan University
Zhou Nie: Hunan University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-57770-1

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