Measurement of Single Molecular Interactions by Dynamic Force Microscopy

Unbinding forces of weak, noncovalent bonds have been measured by scanning force microscopy (1 ) or biomembrane force probes (2 ). Initially, these scanning force microscopy measurements focused on feasibility studies to measure single biomolecular interactions (3 –5 ). Recently, however, a few groups showed that these single molecule experiments give a direct link to bulk experiments where thermodynamic data are experimentally acquired (6 –9 ). In contrast with bulk experiments where averaged properties are measured, a single molecular approach gives access to properties that are hidden in the ensemble. These experiments can give insight into the geometry of the energy landscape of a biomolecular bond (7 ,9 –11 ). Some experiments even showed that intermediate states during unbinding (unfolding) exist which only can be detected by single molecule experiments (12 –14 ).