Probing multivalent interactions in a synthetic host-guest complex by dynamic force spectroscopy. 
Multivalency is present in many biological and synthetic systems.  Successful application of multivalency depends on a correct understanding of the thermodynamics and kinetics of this phenomenon.  In this Article, we address the stability and strength of multivalent bonds with force spectroscopy techniques employing a synthetic adamantane/β-cyclodextrin model system.  Comparing the experimental findings to theoretical predictions for the rupture force and the kinetic off-rate, we find that when the valency of the complex is increased from mono- to di- to trivalent, there is a transition from quasi-equilibrium, with a constant rupture force of 99 pN, to a kinetically dependent state, with loading-rate-dependent rupture forces from 140 to 184 pN (divalent) and 175 to 210 pN (trivalent).  Additional binding geometries, parallel monovalent ruptures, single-bound divalent ruptures, and single- and double-bound trivalent ruptures are identified.  The experimental kinetic off-rates of the multivalent complexes show that the stability of the complexes is significantly enhanced with the number of bonds, in agreement with the predictions of a noncooperative multivalent model.