Force probing ligand-receptor interactions on cells and exosomes

Using the single-molecule force spectroscopy method, we probed dynamic ligand-cellular receptor interactions and found important physical parameters associated with binding and unbinding thermodynamics. First, the rupture force of individual ligand-receptor bonds was unchanged for different cell types. Second, the dissociation dynamics of the binary complex were fitted to the Bell–Evans two-state transition model, in which the kinetic off-rate of multivalent bonds was substantially decreased. Third, sequential rupture events of multiple bonds revealed that the force strength for breaking up the initial bonds under multivalent interactions was weaker than that of synchronous multiple rupture events, but the last rupture events and the force strength were identical to the synchronous case, suggesting an independent parallel bond mechanism. The results provide a wealth of new information on cellular receptors' binding selectivity, affinity, and stability to their ligands.