Nanopore Label-Free Monitoring of B-DNA and Z-DNA Conformational Transition in Real Time.

The transition from right-handed B-DNA to left-handed Z-DNA represents one of the most dramatic structural changes in biology and plays a crucial role in gene expression and transcription. Monitoring this transition is essential for understanding fundamental biological processes, elucidating disease mechanisms, and developing more effective therapeutic strategies. Here, we present a label-free approach to distinguish between Z-DNA and B-DNA by detecting changes in the electrical current modulations as they translocate through a nanopore. This method enables real-time monitoring of B-to-Z and Z-to-B transitions and studying reaction kinetics at the single-molecule level. By directly capturing dynamic structural changes in DNA, our nanopore platform offers a powerful way to investigate DNA structural mechanics and study its interactions with small molecules or therapeutics, thereby advancing the development of versatile tools for studying biologically relevant DNA conformational switches with potential biotechnological applications.