Ligand-receptor binding kinetics in surface plasmon resonance cells: A Monte Carlo analysis

TL;DR

This study uses Monte Carlo simulations to analyze ligand-receptor binding kinetics in SPR cells, revealing significant discrepancies from mean-field predictions due to spatial and temporal correlations, especially at high Damköhler numbers.

Contribution

It demonstrates the failure of mean-field models in SPR kinetics under certain conditions and highlights the importance of spatial-temporal correlations through detailed simulations.

Findings

Mean-field rate estimates deviate significantly from true values in certain regimes.

Spatio-temporal correlations dominate the kinetics at high Damköhler numbers.

Mean-field approximation is inadequate for slow diffusion and high affinity scenarios.

Abstract

Surface plasmon resonance (SPR) chips are widely used to measure association and dissociation rates for the binding kinetics between two species of chemicals, e.g., cell receptors and ligands. It is commonly assumed that ligands are spatially well mixed in the SPR region, and hence a mean-field rate equation description is appropriate. This approximation however ignores the spatial fluctuations as well as temporal correlations induced by multiple local rebinding events, which become prominent for slow diffusion rates and high binding affinities. We report detailed Monte Carlo simulations of ligand binding kinetics in an SPR cell subject to laminar flow. We extract the binding and dissociation rates by means of the techniques frequently employed in experimental analysis that are motivated by the mean-field approximation. We find major discrepancies in a wide parameter regime between the thus extracted rates and the known input simulation values. These results underscore the crucial quantitative importance of spatio-temporal correlations in binary reaction kinetics in SPR cell geometries, and demonstrate the failure of a mean-field analysis of SPR cells in the regime of high Damk\"ohler number Da > 0.1, where the spatio-temporal correlations due to diffusive transport and ligand-receptor rebinding events dominate the dynamics of SPR systems.