Multistage dynamics of Hg2+–DNA interactions: a single-molecule study

Abstract

The metal ion–DNA interaction is key to biochemical processes and has applications in areas such as metal ion sensors and DNA nanomachines. For example, the formation of the T–Hg²⁺–T structure has been used in technologies such as DNA-based mercuric ion sensors. Though the interaction is widely used for practical purposes, the underlying mechanism has not been fully understood. In the present study, we used magnetic tweezers to explore the interactions between λ-DNA and two metal ions, Hg²⁺ and Cd²⁺, at the single-molecule level. Both metal ions caused considerable DNA conformational changes. The resulting DNA compaction dynamics were related to the ion concentration and the exerted force. The increase in the ion concentration promoted DNA compaction, whereas exerting greater forces inhibited this process. Application of a high force generated two-stage dynamics of the Hg²⁺–DNA interaction. However, at a sufficiently high Hg²⁺ concentration, a lower force led to a three-stage process. In contrast, the curves of the binding of Cd²⁺ ions to DNA had a stepwise pattern. Both the AFM scanning results and the single-molecule measurements confirmed that Hg²⁺ influences the DNA conformation in a more pronounced manner than Cd²⁺. The multistage Hg²⁺–DNA interaction was considered to be a result of the different binding mechanisms, including the mismatched base-pair formation. A model was then proposed to explain the peculiar dynamics.