Feeling Inter‐ or Intramolecular Interactions with the Polymer Chain as Probe: Recent Progress in SMFS Studies on Macromolecular Interactions

Single-molecule force spectroscopy (SMFS) opens new avenues for elucidating the structures and functions of large coiled molecules such as synthetic and biopolymers at the single-molecule level. In addition, some of the features in the force-extension curves (i.e. force spectra) are closely related to primary/secondary structures of the molecules being stretched. For example, the long force plateau in the DNA stretching curve is related to the double-helix structure. These features can be regarded as the force fingerprints of individual macromolecules. These force fingerprints can therefore be used as indicators/criteria of single-molecule manipulation during the measurement of some unknown intra- or intermolecular interactions. By comparing the force spectra of a single polymer chain before and after interaction with other molecules, the mode/strength of such molecular interactions can be derived. This Review focuses on recent advances in AFM-based SMFS studies on molecular interactions in both synthetic and biopolymer systems using a single macromolecular chain as probe, including interactions between nucleic acids and proteins, mechanochemistry of covalent bonds, conformation-regulated enzymatic reactions, adsorption and desorption of biopolymers on a flat surface or from the nanopore of a carbon nanotube, and polymer interactions in the condensed state.