Gated Transient Dissipative Dimerization of DNA Tetrahedra Nanostructures for Programmed DNAzymes Catalysis

[Image: see text] Transient dissipative dimerization and transient gated dimerization of DNA tetrahedra nanostructures are introduced as functional modules to emulate transient and gated protein–protein interactions and emergent protein–protein guided transient catalytic functions, operating in nature. Four tetrahedra are engineered to yield functional modules that, in the presence of pre-engineered auxiliary nucleic acids and the nicking enzyme Nt.BbvCI, lead to the fueled transient dimerization of two pairs of tetrahedra. The dynamic transient formation and depletion of DNA tetrahedra are followed by transient FRET signals generated by fluorophore-labeled tetrahedra. The integration of two inhibitors within the mixture of the four tetrahedra and two auxiliary modules, fueling the transient dimerization, results in selective inhibitor-guided gated transient dimerization of two different DNA tetrahedra dimers. Kinetic models for the dynamic transient dimerization and gated transient dimerization of the DNA tetrahedra are formulated and computationally simulated. The derived rate-constants allow the prediction and subsequent experimental validation of the performance of the systems under different auxiliary conditions. In addition, by appropriate modification of the four tetrahedra structures, the triggered gated emergence of selective transient catalytic functions driven by the two pairs of DNA tetrahedra dimers is demonstrated.