Dimensionality of Motion and Binding Valency Govern Receptor-Ligand Kinetics As Revealed by Agent-Based Modeling

Authored by Marc Thilo Figge, Teresa Lehnert

Date Published: 2017

DOI: 10.3389/fimmu.2017.01692

Sponsors: German Federal Ministry of Education and Research (BMBF) German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)

Platforms: C++

Model Documentation: Other Narrative Flow charts

Model Code URLs: Model code not found

Abstract

Mathematical modeling and computer simulations have become an integral part of modern biological research. The strength of theoretical approaches is in the simplification of complex biological systems. We here consider the general problem of receptor ligand binding in the context of antibody antigen binding. On the one hand, we establish a quantitative mapping between macroscopic binding rates of a deterministic differential equation model and their microscopic equivalents as obtained from simulating the spatiotemporal binding kinetics by stochastic agent-based models. On the other hand, we investigate the impact of various properties of B cell-derived receptors such as their dimensionality of motion, morphology, and binding valency on the receptor ligand binding kinetics. To this end, we implemented an algorithm that simulates antigen binding by B cell-derived receptors with a Y-shaped morphology that can move in different dimensionalities, i.e., either as membrane-anchored receptors or as soluble receptors. The mapping of the macroscopic and microscopic binding rates allowed us to quantitatively compare different agent-based model variants for the different types of B cell-derived receptors. Our results indicate that the dimensionality of motion governs the binding kinetics and that this predominant impact is quantitatively compensated by the bivalency of these receptors.
Tags
Agent-based model Ordinary differential equations systems biology activation diffusion Monte-carlo-simulation B-cells Exact stochastic simulation Antibody-antigen binding Receptor-ligand interaction Dimensionality of motion Binding valency Cell synapse formation Coupled chemical-reactions Antigen receptor Affinity