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dc.contributorVirginia Techen_US
dc.contributor.authorGopalakrishnan, Mahimaen_US
dc.contributor.authorForsten-Williams, K.en_US
dc.contributor.authorNugent, M. A.en_US
dc.contributor.authorTauber, U. C.en_US
dc.date.accessioned2014-02-26T19:10:04Z
dc.date.available2014-02-26T19:10:04Z
dc.date.issued2005-12-01
dc.identifier.citationGopalakrishnan, M; Forsten-Williams, K; Nugent, MA; et al., "Effects of receptor clustering on ligand dissociation kinetics: Theory and simulations," Biophysical Journal 89(6), 3686-3700 (2005); doi: 10.1529/biophysj.105.065300
dc.identifier.issn0006-3495
dc.identifier.urihttp://hdl.handle.net/10919/25766
dc.description.abstractReceptor-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 fibrbroblast growth factor-2 (FGF2) from heparan sulfate proteoglycans (HSPGs), co-receptors for FGF-2. In this article, we develop a continuum stochastic formalism to address how receptor clustering might influence 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 nonmonotonic behavior with time. These predictions are verified via lattice Monte Carlo simulations. Comparison with FGF-2-HSPG experimental results is made and suggests that the theory could be used to analyze similar biological systems. We further present an analysis of an additional cooperative internal-diffusion model that might be used by other systems to increase ligand retention when simple rebinding is insufficient.
dc.description.sponsorshipMax Planck Society
dc.description.sponsorshipNational Science Foundation NSF-DMR 0089451, NSF-9875626, NSF-DMR 0308548
dc.description.sponsorshipNational Institutes of Health NIH-HL56200, NIH-HL46902
dc.description.sponsorshipBank of America Jeffress Memorial Trust J-594
dc.language.isoen_US
dc.publisherCELL PRESS
dc.subjectFibroblast-growth-factoren_US
dc.subjectHeparan-sulfate proteoglycansen_US
dc.subjectCell-surfaceen_US
dc.subjectReceptorsen_US
dc.subjectLipid raftsen_US
dc.subjectBound receptorsen_US
dc.subjectRate constantsen_US
dc.subjectBindingen_US
dc.subjectMembranesen_US
dc.subjectDiffusionen_US
dc.subjectCholesterolen_US
dc.titleEffects of receptor clustering on ligand dissociation kinetics: Theory and simulationsen_US
dc.typeArticleen_US
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0006349505730150
dc.date.accessed2014-02-05
dc.title.serialBiophysical Journal
dc.identifier.doihttps://doi.org/10.1529/biophysj.105.065300
dc.type.dcmitypeTexten_US


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