Dynamic Modulation of Multicellular Interactions via ATP-Dissipative DNA Assembly.

Abstract

Living cells exhibit dynamic adaptability through ATP-fueled processes that are crucial for tissue development and immune responses. Conventional methods for controlling cell assembly lack the nonequilibrium, reversible behavior of natural systems. Here, we present an ATP-dissipative DNA assembly system that leverages DNA's programmability to enable adaptive, hierarchical structures with spatiotemporal control. By utilizing various DNA monomers, including double-stranded DNA (dsDNA), tetrahedral DNA frameworks, and branched DNA frameworks, we achieve the precise regulation of cell assembly in response to ATP-driven enzymatic reactions. BDF-based condensates, formed through multivalent liquid-liquid phase separation (LLPS), dynamically modulate intercellular interactions, mimicking the extracellular matrix adaptability. This system was successfully applied to regulate cell assembly in Ramos, PC-12, and natural killer (NK) cells. By harnessing endogenous ATP secreted by cells, we enabled real-time reversible control over cell assembly. Furthermore, the ATP-dissipative assembly system enhanced the tumor-killing efficacy of NK cells by modulating their interactions with cancer cells. This work highlights the potential of DNA-based dissipative self-assembly for precise spatiotemporal regulation of cellular interactions, shedding light on advanced applications in intelligent materials and immunotherapy.