(418e) Information-Theoretic Approach to the Characterization of Tether-Bond Dissociation Kinetics

Single-molecule investigations of the kinetics of receptor-ligand interactions are often conducted using adhesion flow assays. In these assays, cells or beads adhere to surfaces via a small number of receptor-ligand complexes (tether bonds): The highly variable durations are recorded and utilized for the estimation of rate constants. Although this variability presents obstacles to standard methods of data analysis, the data itself is conducive to information-based approaches. Using the stochastic approach to chemical kinetics, we construct the pause time distribution and develop robust maximum likelihood (ML) estimators of both rate constants and models of their force-dependence. We also develop a robust method of distinguishing between the Bell, Dembo and alternative models of the force-dependence of the rate of tether-bond dissociation using Akaike's Information Criterion (AIC). Our findings conclusively demonstrate that ML estimators of adhesion kinetics are substantial improvements over more conventional approaches, and when combined with Fisher Information, they may be used to objectively and reproducibly distinguish the kinetics of different receptor-ligand complexes.