DNA-based cooperative games: an interactive collective decision-making architecture

Game theory provides an architecture for multi-agent strategic interactions, while DNA computing offers programmable, parallel molecular-scale operations, enabling unique "molecular gaming" systems beyond silicon-based architectures. Current approaches, primarily using DNA strand displacement cascades, face limitations such as signal attenuation, asynchrony, and orthogonality challenges due to reaction by-products, hindering scalability and reliability. To address this, we developed a "majority-rule" game-based DNA architecture centered on a Trident Decision Maker (TDM). The TDM integrates a trident-shaped recognition domain for vote sensing and steric protection against Exonuclease Lambda (Exo λ), with a double-stranded signal module that releases outputs via controlled strand displacement and hydrolysis. The TDM game process does not require a cascaded network, enabling synchronous responses to input signals. By leveraging the sequence-nonspecific hydrolysis property of Exo λ, partial by-products were effectively eliminated, while reducing the complexity of orthogonal sequence design required for the input and output strands. Furthermore, through structured programming and modular expansion, we have implemented three advanced gaming strategies-one-vote veto, access control, and decision revocation-thereby fulfilling molecular decision-making functions across a broader range of application scenarios. The TDM is expected to serve as a key node for implementing decision-making tasks in molecular circuits, thereby ensuring their reliable operation. This work establishes a programmable majority-rule game-theoretic platform for molecular systems and is anticipated to open avenues for applications in molecular computing, multi-agent interactions, and biosensing.