Effects of receptor clustering on ligand dissociation kinetics: Theory and simulations

dc.contributor.authorGopalakrishnan, Mahimaen
dc.contributor.authorForsten-Williams, Kimberlyen
dc.contributor.authorNugent, M. A.en
dc.contributor.authorTäuber, Uwe C.en
dc.contributor.departmentPhysicsen
dc.date.accessioned2016-09-30T13:08:51Zen
dc.date.available2016-09-30T13:08:51Zen
dc.date.issued2005-12-01en
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 fibroblast growth factor-2 (FGF-2) from heparan sulfate proteoglycans (HSPG), co-receptors for FGF-2. In this paper, we develop a continuum stochastic formalism in order 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 non-monotonic 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 co-operative “internal diffusion” model that might be used by other systems to increase ligand retention when simple rebinding is insufficient.en
dc.description.versionPublished versionen
dc.format.extent3686 - 3700 (15) page(s)en
dc.identifier.doihttps://doi.org/10.1529/biophysj.105.065300en
dc.identifier.issn0006-3495en
dc.identifier.issue6en
dc.identifier.urihttp://hdl.handle.net/10919/73110en
dc.identifier.volume89en
dc.language.isoenen
dc.publisherCell Pressen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000233590800011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectBiophysicsen
dc.subjectBIOPHYSICSen
dc.subjectFIBROBLAST-GROWTH-FACTORen
dc.subjectHEPARAN-SULFATE PROTEOGLYCANSen
dc.subjectCELL-SURFACE RECEPTORSen
dc.subjectLIPID RAFTSen
dc.subjectBOUND RECEPTORSen
dc.subjectRATE CONSTANTSen
dc.subjectBINDINGen
dc.subjectMEMBRANEen
dc.subjectDIFFUSIONen
dc.subjectCHOLESTEROLen
dc.titleEffects of receptor clustering on ligand dissociation kinetics: Theory and simulationsen
dc.title.serialBiophysical Journalen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/Physicsen

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