Deterministic Mechanical Model of T-Killer Cell Polarization Reproduces the Wandering of Aim between Simultaneously Engaged Targets 英文参考文献.docVIP

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Deterministic Mechanical Model of T-Killer Cell Polarization Reproduces the Wandering of Aim between Simultaneously Engaged Targets 英文参考文献.doc

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Deterministic Mechanical Model of T-Killer Cell Polarization Reproduces the Wandering of Aim between Simultaneously Engaged Targets 英文参考文献

DeterministicMechanicalModelofT-KillerCell PolarizationReproducestheWanderingofAimbetween SimultaneouslyEngagedTargets MunJuKim,IvanV.Maly* DepartmentofComputationalBiology,UniversityofPittsburghSchoolofMedicine,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Abstract T-killer cells of the immune system eliminate virus-infected and tumorous cells through direct cell–cell interactions. ReorientationofthekillingapparatusinsidetheTcelltotheT-cellinterfacewiththetargetcellensuresspecificityofthe immuneresponse.Thekillingapparatuscanalsooscillatenexttothecell–cellinterface.Whentwotargetcellsareengaged bytheTcellsimultaneously,thekillingapparatuscanoscillatebetweenthetwointerfaceareas.Thisoscillationisoneofthe most striking examples of cell movements that give the microscopist an unmechanistic impression of the cell’s fidgety indecision. We have constructed a three-dimensional, numerical biomechanical model of the molecular-motor-driven microtubulecytoskeletonthatpositionsthekillingapparatus.Themodeldemonstratesthatthecorticalpullingmechanism isindeedcapableoforientingthekillingapparatusintothefunctionalpositionunderarangeofconditions.Themodelalso predicts experimentally testable limitations of this commonly hypothesized mechanism of T-cell polarization. After the reorientation, the numerical solution exhibits complex, multidirectional, multiperiodic, and sustained oscillations in the absence of any external guidance or stochasticity. These computational results demonstrate that the strikingly animate wanderingofaiminT-killercellshasapurelymechanicalanddeterministicexplanation. Citation:KimMJ,MalyIV(2009)DeterministicMechanicalModelofT-KillerCellPolarizationReproducestheWanderingofAimbetweenSimultaneouslyEngaged Targets.PLoSComputBiol5(1):e1000260.doi:10.1371/journal.pcbi.1000260 Editor:JasonA.Papin,UniversityofVirginia,UnitedStatesofAmerica ReceivedJuly2,2008;AcceptedNovember24,2008;PublishedJanuary9,2009 Copyright: ? 2009 Kim, Maly. This is an open-access article distribu