Probing DNA-peptide interaction forces at the single-molecule level

The versatility of chemical peptide synthesis combined with the high sensitivity of AFM single-molecule force spectroscopy allows us to investigate, quantify, and control molecular recognition processes (molecular nanotechnology), offering a tremendous potential in chemical biology. Single-molecule force spectroscopy experiments are able to detect fast intermediate transition states, details of the energy landscape, and structural changes, while avoiding multiple binding events that can occur under ensemble conditions. Dynamic force spectroscopy (DFS) is even able to provide data on the complex lifetime. This minireview outlines the biophysical methodology, discusses different experimental set-ups, and presents representative results in the form of two case studies, both dealing with DNA-binding peptides. They may serve as model systems, e.g., for transcription factors or gene transfection agents.