Reliability theory for receptor-ligand bond dissociation

Cell adhesion in the presence of hydrodynamic forces is a critical factor i n inflammation, cancer metastasis, and blood clotting. A number of assays h ave recently been developed to apply forces to small numbers of the recepto r-ligand bonds responsible for adhesion. Examples include assays using hydr odynamic shear in flow chambers or elastic probe deflection assays such as the atomic force microscope or the biomembrane force probe. One wishes to u se the data on the time distribution of dissociation from these assays to d erive information on the force dependence of reaction rates, an important d eterminant of cell adhesive behavior. The dissociation process can be descr ibed using the theory developed for reliability engineering of electronic c omponents and networks. We use this framework along with the Bell model for the reverse reaction rate (k(r) = k(r)(0) exp[r(0) f/kT], where f is the a pplied force and k(r)(0) and r(0) are Bell model parameters) to write close d form expressions for the probability distribution of break-up with multip le independent or interacting bonds. These expressions show that the averag e lifetime of n bonds scales with the nth harmonic number multiplied by the lifetime of a single bond. Results from calculation and simulations are us ed to describe the effect of experimental procedures in forced unbinding as says on the estimation of parameters for the force dependence of reverse re action rates. (C) 2001 American Institute of Physics.