Time-evolution of epitope-paratope bonds investigated by dynamic force spectroscopy

The time-dependent evolution of epitope-paratope bond stability is studied by dynamic force spectroscopy. We show a significant increase in binding strength within seconds of initial association, corresponding to an early stage of bond maturation. A model linking this process to the dynamic lateral movement of antibodies on structured epitope lattices, recently studied with High-Speed AFM, is proposed. Antibodies show a bipedal walking behavior with step periods of ~40ms on such lattices, and our results indicate that these rapid cycles of association and dissociation interrupt the process of bond maturation. Consequently, epitope-paratope interactions are perpetually trapped in a weakly bound state and cannot transition into the fully docked state.