Tetrahedral DNA framework-directed hybridization chain reaction controlled self-assembly

Nonenzymatic isothermal nucleic acid self-assembly techniques (e.g., the hybridization chain reaction, HCR) hold potential in building materials and biological sensing. However, a traditional HCR is triggered by the random diffusion and disordered conformations of ssDNA initiators, resulting in asynchronous initiation and inherently highly heterogeneous products that do not meet the standards of well-defined nanomaterials. Herein, we developed a nanomechanical restricted strategy directed by tetrahedral DNA frameworks (TDFs) to control HCR self-assembly. We found that the restricted initiator at TDF vertices could induce DNA hairpin assembly to form homogeneous products in solution. Mechanistically, we found that TDFs accelerated the strand displacement rate of the starting H1 and synchronized the assembly process of the HCR. Furthermore, the TDF exhibited strict vertex specificity for HCR controllable assembly, and side extension of the initiator could not result in homogeneous products. This work presents a straightforward and efficient approach for controlling the living self-assembly of macromolecular DNA, thus providing a novel tool for HCR-based nanomanufacturing and quantitative sensing applications.