Force-Induced Visualization of Nucleic Acid Functions with Single-Nucleotide Resolution

Nucleic acids are major targets for molecular sensing because of their wide involvement in biological functions. Determining their presence, movement, and binding specificity is thus well pursued. However, many current techniques are usually sophisticated, expensive, and often lack single-nucleotide resolution. In this paper, we report the force-induced visualization method that relies on the novel concept of mechanical force to determine the functional positions of nucleic acids with single-nucleotide resolution. The use of an adjustable mechanical force overcomes the variation of analyte concentration and differences in buffer conditions that are common in biological settings. Two examples are described to validate the method: one is probing the mRNA movement during ribosomal translocation, and the other is revealing the interacting sites and strengths of DNA-binding drugs based on the force amplitude. The flexibility of the method, simplicity of the associated device, and capability of multiplexed detection will potentially enable a broad range of biomedical applications.