IMA Journal of Applied Mathematics Advance Access originally published online on November 1, 2007
IMA Journal of Applied Mathematics 2007 72(6):865-893; doi:10.1093/imamat/hxm041
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Steric hindrance effects in thin reaction zones: applications to BIAcore

Department of Mathematical Sciences, University of Delaware, Newark, DE 19716-2553, USA
Email: edwards{at}math.udel.edu
Received on August 15, 2006; Accepted on July 27, 2007
Many biological and industrial processes have reactions which occur in thin zones of densely packed receptors. Understanding the rate of such reactions is important, and the BIAcore surface plasmon resonance biosensor for measuring rate constants has such a geometry. However, interpreting biosensor data correctly is difficult since large ligand molecules can block multiple receptor sites, thus skewing the kinetics. General mathematical principles are presented for handling this phenomenon, and a receptor layer model is presented explicitly. An integro-partial differential equation results. Using perturbation techniques, the problem can be simplified somewhat. In the limit of small Damköhler number, the non-local nature of the system becomes evident in the association problem, while other experiments can be modelled using local techniques. Explicit and asymptotic solutions are constructed for large-molecule cases motivated by experimental design. The analysis provides insight into surface–volume reactions occurring in various contexts. In particular, this steric hindrance effect can often be quantified with a single dimensionless parameter.
Keywords: biomolecular reactions; rate constants; asymptotics; integrodifferential equations; steric hindrance effects; BIAcore.