Title:
Flow-enhanced adhesion regulated by a selectin interdomain hinge

dc.contributor.author Lou, Jizhong en_US
dc.contributor.author Yago, Tadayuki en_US
dc.contributor.author Klopocki, Arkadiusz G. en_US
dc.contributor.author Mehta, Padmaja en_US
dc.contributor.author Chen, Wei en_US
dc.contributor.author Zarnitsyna, Veronika I. en_US
dc.contributor.author Bovin, Nicolai V. en_US
dc.contributor.author Zhu, Cheng en_US
dc.contributor.author McEver, Rodger P. en_US
dc.contributor.corporatename Oklahoma Medical Research Foundation. Cardiovascular Biology Research Program en_US
dc.contributor.corporatename University of Oklahoma Health Sciences Center. Dept. of Biochemistry and Molecular Biology en_US
dc.contributor.corporatename Georgia Institute of Technology. Institute for Bioengineering and Bioscience en_US
dc.contributor.corporatename Georgia Institute of Technology. Dept. of Biomedical Engineering en_US
dc.contributor.corporatename Emory University. Dept. of Biomedical Engineering en_US
dc.contributor.corporatename Georgia Institute of Technology. School of Mechanical Engineering en_US
dc.contributor.corporatename Institut bioorganicheskoĭ khimii im. M.M. Shemi︠a︡kina i I︠U︡. A. Ovchinnikova en_US
dc.date.accessioned 2013-06-03T20:16:36Z
dc.date.available 2013-06-03T20:16:36Z
dc.date.issued 2006-09
dc.description © 2006 The Authors en_US
dc.description The electronic version of this article is the complete one and can be found online at: http://www.jcb.org/cgi/doi/10.1083/jcb.200606056 en_US
dc.description DOI: 10.1083/jcb.200606056 en_US
dc.description.abstract L-selectin requires a threshold shear to enable leukocytes to tether to and roll on vascular surfaces. Transport mechanisms govern flow-enhanced tethering, whereas force governs fl ow-enhanced rolling by prolonging the lifetimes of L-selectin–ligand complexes (catch bonds). Using selectin crystal structures, molecular dynamics simulations, site-directed mutagenesis, single-molecule force and kinetics experiments, Monte Carlo modeling, and flow chamber adhesion studies, we show that eliminating a hydrogen bond to increase the fl exibility of an interdomain hinge in L-selectin reduced the shear threshold for adhesion via two mechanisms. One affects the on-rate by increasing tethering through greater rotational diffusion. The other affects the off-rate by strengthening rolling through augmented catch bonds with longer lifetimes at smaller forces. By forcing open the hinge angle, ligand may slide across its interface with L-selectin to promote rebinding, thereby providing a mechanism for catch bonds. Thus, allosteric changes remote from the ligand-binding interface regulate both bond formation and dissociation. en_US
dc.identifier.citation Lou J., Yago T., Klopocki A.G., Mehta P., Chen W., Zarnitsyna V.I., Bovin N.V., Zhu C., McEver R.P. "Flow-enhanced adhesion regulated by a selectin interdomain hinge," Journal of cell biology, 174, 7, 1107-1117 (September 25 2006) en_US
dc.identifier.doi 10.1083/jcb.200606056
dc.identifier.issn 0021-9525
dc.identifier.uri http://hdl.handle.net/1853/47160
dc.language.iso en_US en_US
dc.publisher Georgia Institute of Technology en_US
dc.publisher.original Rockefeller University Press en_US
dc.subject Interdomain hinge en_US
dc.subject Ligands en_US
dc.subject L-selectin en_US
dc.subject Monte Carlo simulations en_US
dc.subject P-selectin en_US
dc.subject Shear threshold en_US
dc.subject Adhesion en_US
dc.title Flow-enhanced adhesion regulated by a selectin interdomain hinge en_US
dc.type Text
dc.type.genre Article
dspace.entity.type Publication
local.contributor.author Zhu, Cheng
local.contributor.corporatename Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename College of Engineering
relation.isAuthorOfPublication d28f1a84-f07d-40ec-bed3-60bc4c140551
relation.isOrgUnitOfPublication da59be3c-3d0a-41da-91b9-ebe2ecc83b66
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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