DNA Artificial Mechanoreceptor-Programmed Dual-Mode Biosensor for Highly Sensitive MicroRNA Detection via Spatially Confined Catalytic Assembly and MOF-Derived Nanozymes.

The integration of synthetic DNA receptors with metal-organic framework (MOF)-derived materials to construct synchronous dual-mode biosensors remains a challenging yet underexplored frontier. Herein, we report a novel DNA artificial mechanoreceptor (DAMR) engineered to enable synchronous fluorescence and colorimetric signal outputs upon target-induced mechanical actuation. In the fluorescence mode, the DAMR platform synergistically incorporates magnetic separation, DNA conjugate interface engineering, and a spatially confined catalytic hairpin assembly (CHA) as a mechanical switch for microRNA input. This switch exhibits tunable sensitivity and initiates dynamic DNA assembly via the release of fuel primers. The released fuel primers subsequently drive an autocatalytic assembly circuit (AAC), leading to fluorescence signal activation through fluorescence resonance energy transfer (FRET) within the hairpin probes. In the parallel colorimetric mode, target recognition triggers the hybridization-mediated assembly of a biotin-labeled complex on magnetic beads, which further recruits streptavidin-functionalized Fe-Co-MOF nanozymes. The Fe-Co MOF, exhibiting potent peroxidase-like activity, catalyzes the oxidation of TMB, generating a colorimetric signal whose intensity correlates with the target concentration. The uniqueness of this system stems from the strategic combination of magnetic beads, Fe-Co MOF nanozymes, and programmable DNA hairpin assemblies. This integration effectively mitigates matrix interference from proteases, eliminates the need for complex sample pretreatment, and enhances the overall biosensing robustness. Furthermore, the incorporation of MOF-derived materials with DNA receptors significantly improves the biostability and accelerates reaction kinetics. The modular design of DAMR also allows for the reprogramming of recognition sequences, extending the applicability of this method to diverse microRNAs and other nucleic acid targets. This work demonstrates a versatile and powerful approach for dual-signal transduction based on DNA mechanical receptors, holding considerable promise for advancements in mechanobiology, biosensor development, and biomedical diagnostics.