dorsal/arxiv
View SchemaEffects of receptor clustering on ligand dissociation: Theory and simulations
| Authors | Manoj Gopalakrishnan, Kimberly Forsten-Williams, Matthew A. Nugent, Uwe C. Tauber |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0407015 |
| URL | https://arxiv.org/abs/q-bio/0407015 |
| DOI | 10.1529/biophysj.105.065300 |
| Journal | Biophys. J. 89 (2005) 3685 |
Abstract
Receptor-ligand binding is a critical first step in signal transduction and the duration of the interaction can impact signal generation. In mammalian cells, clustering of receptors may be facilitated by heterogeneous zones of lipids, known as lipid rafts. In vitro experiments show that disruption of rafts significantly alters the dissociation of fibroblast growth factor-2 (FGF-2) from heparan sulfate proteoglycans, co-receptors for FGF-2. In this paper, we develop a continuum stochastic formalism in order to (i) study how rebinding affects the dissociation of ligands from a planar substrate, and (ii) address the question of how receptor clustering influences ligand rebinding. We find that clusters reduce the effective dissociation rate dramatically when the clusters are dense and the overall surface density of receptors is low. The effect is much less pronounced in the case of high receptor density and shows non-monotonic behavior with time. These predictions are verified via lattice Monte Carlo simulations. Comparison with experimental results suggests that the theory does not capture the complete biological system. We speculate that additional co-operative mechanisms might be present in order to increase ligand retention, and present one possible ``internal diffusion'' model.
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"abstract": "Receptor-ligand binding is a critical first step in signal transduction and\nthe duration of the interaction can impact signal generation. In mammalian\ncells, clustering of receptors may be facilitated by heterogeneous zones of\nlipids, known as lipid rafts. In vitro experiments show that disruption of\nrafts significantly alters the dissociation of fibroblast growth factor-2\n(FGF-2) from heparan sulfate proteoglycans, co-receptors for FGF-2. In this\npaper, we develop a continuum stochastic formalism in order to (i) study how\nrebinding affects the dissociation of ligands from a planar substrate, and (ii)\naddress the question of how receptor clustering influences ligand rebinding. We\nfind that clusters reduce the effective dissociation rate dramatically when the\nclusters are dense and the overall surface density of receptors is low. The\neffect is much less pronounced in the case of high receptor density and shows\nnon-monotonic behavior with time. These predictions are verified via lattice\nMonte Carlo simulations. Comparison with experimental results suggests that the\ntheory does not capture the complete biological system. We speculate that\nadditional co-operative mechanisms might be present in order to increase ligand\nretention, and present one possible ``internal diffusion\u0027\u0027 model.",
"arxiv_id": "q-bio/0407015",
"authors": [
"Manoj Gopalakrishnan",
"Kimberly Forsten-Williams",
"Matthew A. Nugent",
"Uwe C. Tauber"
],
"categories": [
"q-bio.SC",
"cond-mat.stat-mech",
"q-bio.CB"
],
"doi": "10.1529/biophysj.105.065300",
"journal_ref": "Biophys. J. 89 (2005) 3685",
"title": "Effects of receptor clustering on ligand dissociation: Theory and simulations",
"url": "https://arxiv.org/abs/q-bio/0407015"
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