Reversible Ligand–Receptor Interaction-Induced “Tango”-like Dancing of Nanodisks on Living Cell Membrane

Real-time tracking of the kinetic binding processes of individual nanocargos on living cell membranes is essential for a better understanding of the cellular translocation mechanism and further optimization of the delivery functionality. In this work, we directly monitored the dynamic ligand–receptor interaction-modulated translational motions of two-dimensional (2D) nanocargos (gold nanodisks, Au NDs) on a living cell membrane. “Tango”-like diffusion is observed, where the nanocargos experience transitions between fast long-step searching and occasional restricted translational motion on the lipid membrane. From the single-particle tracking results, directional motion is involved in the long-range searching process, while tilted shaking dominates the restricted motion. Upon thoroughly analyzing the molecular binding free energy from the diffusion tracks, alternative bindings are clearly noted and closely associated with the transitions in different diffusion modes. These interesting observations provide deep insight into the translocation mechanism of 2D nanocargo in living cells.