Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell-surface receptor aggregates

Michael I. Monine, Richard G Posner, Paul B. Savage, James R. Faeder, William S. Hlavacek

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We use flow cytometry to characterize equilibrium binding of a fluorophore-labeled trivalent model antigen to bivalent IgE-FcεRI complexes on RBL cells. We find that flow cytometric measurements are consistent with an equilibrium model for ligand-receptor binding in which binding sites are assumed to be equivalent and ligand-induced receptor aggregates are assumed to be acyclic. However, this model predicts extensive receptor aggregation at antigen concentrations that yield strong cellular secretory responses, which is inconsistent with the expectation that large receptor aggregates should inhibit such responses. To investigate possible explanations for this discrepancy, we evaluate four rule-based models for interaction of a trivalent ligand with a bivalent cell-surface receptor that relax simplifying assumptions of the equilibrium model. These models are simulated using a rule-based kinetic Monte Carlo approach to investigate the kinetics of ligand-induced receptor aggregation and to study how the kinetics and equilibria of ligand-receptor interaction are affected by steric constraints on receptor aggregate configurations and by the formation of cyclic receptor aggregates. The results suggest that formation of linear chains of cyclic receptor dimers may be important for generating secretory signals. Steric effects that limit receptor aggregation and transient formation of small receptor aggregates may also be important.

Original languageEnglish (US)
Pages (from-to)48-56
Number of pages9
JournalBiophysical Journal
Volume98
Issue number1
DOIs
StatePublished - Jan 6 2010

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Cell Surface Receptors
Receptor Aggregation
Ligands
Antigens
Immunoglobulin E
Flow Cytometry
Binding Sites

ASJC Scopus subject areas

  • Biophysics

Cite this

Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell-surface receptor aggregates. / Monine, Michael I.; Posner, Richard G; Savage, Paul B.; Faeder, James R.; Hlavacek, William S.

In: Biophysical Journal, Vol. 98, No. 1, 06.01.2010, p. 48-56.

Research output: Contribution to journalArticle

Monine, Michael I. ; Posner, Richard G ; Savage, Paul B. ; Faeder, James R. ; Hlavacek, William S. / Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell-surface receptor aggregates. In: Biophysical Journal. 2010 ; Vol. 98, No. 1. pp. 48-56.
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