Paper detail

Determination of single-bond association kinetics by tethered particle motion: concept and simulations

Tethered particle motion (TPM) --- the motion of a micro- or nanoparticle tethered to a substrate by a macromolecule --- is a system that has proven extremely useful for its ability to reveal physical features of the tether, because the thermal motion of the bound particle reports sensitively on parameters like the length, the rigidity, or the folding state of its tether. In this paper, we discuss a novel application of TPM, surveying its utility in probing the kinetics of single secondary bonds: bonds that form and break between the tethered particle and a substrate due, for instance, to receptor/ligand pairs on particle and substrate. Much like the tether itself affects the motion pattern, so do the presence and absence of such secondary connections. Keeping the tether properties constant, we demonstrate how raw positional TPM data may be parsed to generate detailed insights into the association and dissociation kinetics of single secondary bonds. We do this using coarse-grained molecular dynamics simulations, specifically developed to treat the motion of particles close to interfaces.