On the dynamic behaviour of the forced dissociation of ligand-receptor pairs

Measurement of the forced rupture of biotin from streptavidin, using the force microscope, revealed a logarithmic dependence on the rate of loading. Transition state theory predicts that the rupture force is dependent on the rate of force loading and the dissociation rate constant of the interaction. Analysis of the dependence of the rupture force with loading rate reveals that the barrier to unbinding under the loading rates employed here is situated between 0.12 and 0.18 nm away from the bound state. The position of the barrier determined is similar in value to the results obtained using complementary force techniques, and is matched by calculations from computational simulation. Thus, force rupture measurements may be used to profile the internal energy pathway of molecular dissociation events. The results suggest, however, that the loading rates employed here, using cantilever retract velocities as low as 1 nm s-1, are still too high to explore the whole of the unbinding energy landscape, and suggests further avenues for instrumental and experimental development.