In recent decades, atomic force microscopy (AFM), in particular the force spectroscopy mode, has become a method of choice to study biomolecular interactions at the single-molecule level. However, grafting procedures as well as determining binding specificity remain challenging. We report here an innovative approach based on a photocleavable group that enables in situ release of the ligands bound to the AFM tip and thus allows direct assessment of the binding specificity. Applicable to a wide variety of molecules, the strategy presented here provides new opportunities to study specific interactions and deliver single molecules with high spatiotemporal resolution in a wide range of applications, including AFM-based cell biology.
Koehler, M., Lo Giudice, C., Vogl, P., Ebner, A., Hinterdorfer, P., Gruber, H. J., & Alsteens, D. (2020). Control of Ligand-Binding Specificity Using Photocleavable Linkers in AFM Force Spectroscopy. Nano Letters : a journal dedicated to nanoscience and nanotechnology, 20(5), 4038-4042. https://doi.org/10.1021/acs.nanolett.0c01426 (Original work published 2020)