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dc.contributor.authorParadise, Ranjani K.
dc.contributor.authorLauffenburger, Douglas A.
dc.contributor.authorVan Vliet, Krystyn J.
dc.date.accessioned2011-06-09T15:02:47Z
dc.date.available2011-06-09T15:02:47Z
dc.date.issued2011-01
dc.date.submitted2010-09
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1721.1/63601
dc.description.abstractAcidic extracellular pH is characteristic of the cell microenvironment in several important physiological and pathological contexts. Although it is well established that acidic extracellular pH can have profound effects on processes such as cell adhesion and migration, the underlying molecular mechanisms are largely unknown. Integrin receptors physically connect cells to the extracellular matrix, and are thus likely to modulate cell responses to extracellular conditions. Here, we examine the role of acidic extracellular pH in regulating activation of integrin [alpha]v[beta]3. Through computational molecular dynamics simulations, we find that acidic extracellular pH promotes opening of the [alpha]v[beta]3 headpiece, indicating that acidic pH can thereby facilitate integrin activation. This prediction is consistent with our flow cytometry and atomic force microscope-mediated force spectroscopy assays of integrin [alpha]v[beta]3 on live cells, which both demonstrate that acidic pH promotes activation at the intact cell surface. Finally, quantification of cell morphology and migration measurements shows that acidic extracellular pH affects cell behavior in a manner that is consistent with increased integrin activation. Taken together, these computational and experimental results suggest a new and complementary mechanism of integrin activation regulation, with associated implications for cell adhesion and migration in regions of altered pH that are relevant to wound healing and cancer.en_US
dc.description.sponsorshipNational Institute of Biomedical Imaging and Bioengineering (U.S.) (Award Number T32EB006348)en_US
dc.description.sponsorshipMassachusetts Institute of Technology (Collamore-Rogers Fellowship)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Cell Migration Consortium Grant U54-GM069668)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (CAREER Award)en_US
dc.description.sponsorshipSingapore-MIT Alliance for Research and Technology (BioSystem and Micromechanics (BioSyM) Interdisciplinary Research Group)en_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pone.0015746en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en_US
dc.sourcePLoSen_US
dc.titleAcidic Extracellular pH Promotes Activation of Integrin [alpha]v[beta]3en_US
dc.title.alternativeAcidic Extracellular pH Promotes Activation of Integrin αvβ3en_US
dc.typeArticleen_US
dc.identifier.citationParadise RK, Lauffenburger DA, Van Vliet KJ, 2011 "Acidic Extracellular pH Promotes Activation of Integrin αvβ3." PLoS ONE 6(1): e15746.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Materials Science and Engineeringen_US
dc.contributor.approverVan Vliet, Krystyn J.
dc.contributor.mitauthorParadise, Ranjani K.
dc.contributor.mitauthorLauffenburger, Douglas A.
dc.contributor.mitauthorVan Vliet, Krystyn J.
dc.relation.journalPLoS ONEen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsParadise, Ranjani K.; Lauffenburger, Douglas A.; Van Vliet, Krystyn J.en
dc.identifier.orcidhttps://orcid.org/0000-0001-5735-0560
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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