Quantification of Cell Edge Velocities and Traction Forces Reveals Distinct Motility Modules during Cell Spreading 英文参考文献.docVIP

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Quantification of Cell Edge Velocities and Traction Forces Reveals Distinct Motility Modules during Cell Spreading 英文参考文献.doc

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Quantification of Cell Edge Velocities and Traction Forces Reveals Distinct Motility Modules during Cell Spreading 英文参考文献

QuantificationofCellEdgeVelocitiesandTractionForces RevealsDistinctMotilityModulesduringCellSpreading BenjaminJ.Dubin-Thaler1,2.*,JakeM.Hofman3,4.,YunfeiCai1,HarryXenias1,IngridSpielman1,AnnaV. Shneidman1,LawrenceA.David5,Hans-Gu¨ntherDo¨bereiner1,6,ChrisH.Wiggins4,MichaelP.Sheetz1 1DepartmentofBiologicalSciences,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica,2CellMotionLaboratories,Inc.,NewYork,NewYork,United StatesofAmerica,3DepartmentofPhysics,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica,4DepartmentofAppliedPhysicsandAppliedMath, ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica,5DepartmentofBiomedicalEngineering,ColumbiaUniversity,NewYork,NewYork,UnitedStatesof America,6Universita¨t Bremen,Institutfu¨rBiophysik,Bremen,Germany Abstract Actin-basedcellmotilityandforcegenerationarecentraltoimmuneresponse,tissuedevelopment,andcancermetastasis, andunderstandingactincytoskeletonregulationisamajorgoalofcellbiologists.Cellspreadingisacommonlyusedmodel system for motility experiments – spreading fibroblasts exhibit stereotypic, spatially-isotropic edge dynamics during a reproduciblesequenceoffunctionalphases:1)Duringearlyspreading,cellsforminitialcontactswiththesurface.2)The middle spreading phase exhibits rapidly increasing attachment area. 3) Late spreading is characterized by periodic contractions and stable adhesions formation. While differences in cytoskeletal regulation between phases are known, a globalanalysisofthespatialandtemporalcoordinationofmotilityandforcegenerationismissing.Implementingimproved algorithmsforanalyzingedgedynamicsovertheentirecellperiphery,weobservedthatasingledomainofhomogeneous cytoskeletaldynamicsdominatedeachofthethreephasesofspreading.Thesedomainsexhibitedauniquecombinationof biophysicalandbiochemicalparameters–amotilitymodule.Biophysicalcharacterizationofthemotilitymodulesrevealed that the early phase was dominated by periodic, rapid membrane blebbing; the middle phase exhibited continuous protrusionwithv