Probing drug-DNA interactions using super-resolution force spectroscopy.

Atomic magnetometry and ultrasound, as individual techniques, have been used extensively in various physical, chemical, and biomedical fields. Their combined application, however, has been rare. We report that super-resolution force spectroscopy, which is based on the integration of the two techniques, can find unique biophysical applications in studying drug-DNA interactions. The precisely controlled ultrasound generates acoustic radiation force on the biological systems labeled with magnetic microparticles. A decrease in the magnetic signal, measured by an automated atomic magnetometer, indicates that the acoustic radiation force equals the binding force of the biological system. With 0.5 pN force resolution, we were able to precisely resolve three small molecules binding with two DNA sequences and quantitatively reveal the effect of a single hydrogen bond. Our results indicate that the increases in DNA binding force caused by drug binding correlate with the enthalpy instead of free energy, thus providing an alternative physical parameter for optimizing chemotherapeutic drugs.