Dynamic Modulation of Multicellular Interactions via ATP-Dissipative DNA Assembly

Area of Science:

• Biomaterials Science
• Synthetic Biology
• Molecular Engineering

Background:

• Living cells display dynamic adaptability via ATP-dependent processes vital for development and immunity.
• Current cell assembly control methods lack the nonequilibrium and reversible nature of biological systems.

Purpose of the Study:

• To engineer a novel ATP-dissipative DNA assembly system for spatiotemporal control of cell interactions.
• To create adaptive, hierarchical cellular structures mimicking natural biological systems.

Main Methods:

• Utilized programmable DNA monomers (dsDNA, tetrahedral DNA frameworks, branched DNA frameworks) for precise cell assembly.
• Employed ATP-driven enzymatic reactions and liquid-liquid phase separation (LLPS) for dynamic control.
• Applied the system to Ramos, PC-12, and natural killer (NK) cells, harnessing endogenous ATP.

Main Results:

• Achieved precise, real-time, reversible control over cell assembly using the ATP-dissipative system.
• Demonstrated dynamic modulation of intercellular interactions via branched DNA framework (BDF)-based condensates.
• Showcased enhanced tumor-killing efficacy of NK cells through modulated interactions with cancer cells.

Conclusions:

• The DNA-based dissipative self-assembly system offers precise spatiotemporal regulation of cellular interactions.
• This approach holds significant potential for advanced applications in intelligent materials and immunotherapy.
• The system's ability to harness endogenous ATP enables dynamic and reversible control of cellular behavior.