Single-molecule motions enable direct visualization of biomolecular interactions in solution

Biomolecular interactions are generally accompanied by modifications in size and charge of biomolecules at the nanometer scale. Here we describe a single-molecule method to sense these changes in real time based on statistical learning of diffusive and electric field-induced motion parameters of a trapped molecule in solution. We demonstrate the approach by resolving a monomer-trimer mixture along a protein dissociation pathway and visualizing the binding-unbinding kinetics of a single DNA molecule.