Mapping DNA Conformations Using Single-Molecule Conductance Measurements

DNA is an attractive material for a range of applications in nanoscience and nanotechnology, and it has recently been demonstrated that the electronic properties of DNA are uniquely sensitive to its sequence and structure, opening new opportunities for the development of electronic DNA biosensors. In this report, we examine the origin of multiple conductance peaks that can occur during single-molecule break-junction (SMBJ)-based conductance measurements on DNA. We demonstrate that these peaks originate from the presence of multiple DNA conformations within the solutions, in particular, double-stranded B-form DNA (dsDNA) and G-quadruplex structures. Using a combination of circular dichroism (CD) spectroscopy, computational approaches, sequence and environmental controls, and single-molecule conductance measurements, we disentangle the conductance information and demonstrate that specific conductance values come from specific conformations of the DNA and that the occurrence of these peaks can be controlled by controlling the local environment. In addition, we demonstrate that conductance measurements are uniquely sensitive to identifying these conformations in solutions and that multiple configurations can be detected in solutions over an extremely large concentration range, opening new possibilities for examining low-probability DNA conformations in solutions.

Automated summary

DNA has unique electronic properties that are sensitive to its sequence and structure, making it an attractive material for electronic DNA biosensors. This study investigates the origin of multiple conductance peaks in single-molecule break-junction measurements on DNA and demonstrates that these peaks come from different DNA conformations, such as double-stranded B-form DNA and G-quadruplex structures. By using various techniques and controls, the study shows that specific conductance values correspond to specific DNA conformations and that the occurrence of these conductance peaks can be controlled by the local environment.