Dynamics and dose response in scaffold ligand binding

Abstract

This paper considers systems in which two or more ligands bind independently to a common scaffold. Such systems arise in a range of applications, including immunotherapy and synthetic biology. We show that each stoichiometric compatibility class contains a unique steady state, and that this steady state is asymptotically stable. The main result gives a rigorous proof that the steady-state concentration of the fully bound complex, viewed as a function of the total scaffold concentration, has a unique maximum. This biphasic dose response is a characteristic feature of scaffolding systems and, in the special case of two ligands, plays an important role in the design and analysis of bispecific antibody drugs.