2023
Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton
Amiri S, Muresan C, Shang X, Huet-Calderwood C, Schwartz M, Calderwood D, Murrell M. Intracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton. Nature Communications 2023, 14: 8011. PMID: 38049429, PMCID: PMC10695988, DOI: 10.1038/s41467-023-43612-5.Peer-Reviewed Original ResearchConceptsF-actin architectureStress fibersCortical actinActin cytoskeletonMolecular tension sensorsF-actin stress fibersF-actin cytoskeletonFilamentous actin cytoskeletonMechanical forcesTension sensorCell divisionCytoskeletonCell migrationExtracellular matrixMyosin inhibitionActinDirection of stretchCellsCell axisUniaxial stretchStretchFRET
2021
Early events in endothelial flow sensing
Tanaka K, Joshi D, Timalsina S, Schwartz MA. Early events in endothelial flow sensing. Cytoskeleton 2021, 78: 217-231. PMID: 33543538, DOI: 10.1002/cm.21652.Peer-Reviewed Original ResearchMeSH KeywordsCytoskeletonEndothelial CellsMechanotransduction, CellularSignal TransductionStress, MechanicalConceptsFluid shear stressLymphatic endothelial cellsEndothelial cellsCytoskeletal pathwaysVascular morphogenesisBiochemical signalsGene expressionEC phenotypeLymphatic fluid flowEarly eventsPhysiologyImmediate mechanismPrimary mechanismRecent advancesMorphogenesisMechanotransductionSignalingPhenotypePathwayMechanismExpressionFlow sensingCellsImportant questions
2019
MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation
Hu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.Peer-Reviewed Original ResearchConceptsCell fate reprogrammingChromatin accessibilityActin cytoskeletonSomatic cell reprogrammingPluripotency transcription factorsGlobal chromatin accessibilityGenomic accessibilityCytoskeleton (LINC) complexCell reprogrammingCytoskeletal genesTranscription factorsReprogrammingPluripotencyChromatinCytoskeletonMKL1Unappreciated aspectPathwayNuclear volumeNucleoskeletonSUN2CellsActivationGenesExpression
2018
Local Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at the Nanometer Scale
Kumar A, Anderson KL, Swift MF, Hanein D, Volkmann N, Schwartz MA. Local Tension on Talin in Focal Adhesions Correlates with F-Actin Alignment at the Nanometer Scale. Biophysical Journal 2018, 115: 1569-1579. PMID: 30274833, PMCID: PMC6372196, DOI: 10.1016/j.bpj.2018.08.045.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCells, CulturedCytoskeletonFocal AdhesionsMechanotransduction, CellularMiceMice, KnockoutTalinConceptsActin organizationLocal actin organizationTalin tension sensorFocal adhesion dynamicsLinear actin filamentsIndividual focal adhesionsCellular force transmissionF-actin alignmentFocal adhesionsAdhesion dynamicsCell centerVinculin localizationActin intensityActin filamentsF-actinAdhesion centersNormal physiologyTalinSame cellsAdhesion correlatesStable adhesionTension sensor
2015
ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation
Tornavaca O, Chia M, Dufton N, Almagro LO, Conway DE, Randi AM, Schwartz MA, Matter K, Balda MS. ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation. Journal Of Cell Biology 2015, 208: 821-838. PMID: 25753039, PMCID: PMC4362456, DOI: 10.1083/jcb.201404140.Peer-Reviewed Original ResearchMeSH KeywordsActomyosinAdherens JunctionsAnimalsAntigens, CDCadherinsCapillary PermeabilityCell Adhesion MoleculesCell MovementCells, CulturedClaudin-5Cytoskeletal ProteinsCytoskeletonEndothelial CellsHumansMechanotransduction, CellularMice, Inbred C57BLMyosinsNeovascularization, PhysiologicProtein TransportReceptors, Cell SurfaceTight JunctionsZonula Occludens-1 ProteinConceptsCell-cell tensionAdherens junctionsActive myosin IIZO-1VE-cadherinBarrier formationEndothelial adherens junctionsJunctional recruitmentPrimary endothelial cellsCadherin complexActomyosin organizationCentral regulatorStress fibersInhibition of ROCKMyosin IIProtein ZO-1Tight junction protein ZO-1Cell migrationIntercellular junctionsP114RhoGEFMechanotransducersTight junctionsEndothelial junctionsEndothelial cellsTight junction disruption
2014
Mechanotransduction and extracellular matrix homeostasis
Humphrey JD, Dufresne ER, Schwartz MA. Mechanotransduction and extracellular matrix homeostasis. Nature Reviews Molecular Cell Biology 2014, 15: 802-812. PMID: 25355505, PMCID: PMC4513363, DOI: 10.1038/nrm3896.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytoskeletonExtracellular MatrixHomeostasisHumansIntegrinsMechanotransduction, Cellular
2013
Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1
Conway DE, Breckenridge MT, Hinde E, Gratton E, Chen CS, Schwartz MA. Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1. Current Biology 2013, 23: 1024-1030. PMID: 23684974, PMCID: PMC3676707, DOI: 10.1016/j.cub.2013.04.049.Peer-Reviewed Original ResearchConceptsFluid shear stressVE-cadherinCell-cell junctionsPECAM-1Junctional tensionCytoskeletal remodelingVascular morphogenesisGene expressionComplex consistingCells triggersFlow-dependent vascular remodelingIon channelsFRET measurementsEndothelial cells triggersMechanical tensionNormal vascular functionTension sensorDetectable tensionEC responseStatic cultureJunctional receptorsRemodelingCytoskeletonMorphogenesisVascular remodeling
2010
Integrins and Extracellular Matrix in Mechanotransduction
Schwartz MA. Integrins and Extracellular Matrix in Mechanotransduction. Cold Spring Harbor Perspectives In Biology 2010, 2: a005066. PMID: 21084386, PMCID: PMC2982167, DOI: 10.1101/cshperspect.a005066.Peer-Reviewed Original ResearchConceptsIntegrin-mediated adhesionExtracellular matrixCytoskeletal linker proteinExtracellular matrix fibrilsIntracellular actin filamentsLinker proteinGenetic programActin filamentsExtracellular structuresCell survivalMatrix fibrilsIntegrinsCell functionCurrent knowledgeMechanotransductionMechanical forcesTransmits forcesIntracellularAdhesionCellsCytoskeletonProteinRegulationPathwayEnvironmental forcesCell adhesion: integrating cytoskeletal dynamics and cellular tension
Parsons JT, Horwitz AR, Schwartz MA. Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nature Reviews Molecular Cell Biology 2010, 11: 633-643. PMID: 20729930, PMCID: PMC2992881, DOI: 10.1038/nrm2957.Peer-Reviewed Original ResearchConceptsRho GTPasesGuanine nucleotide exchange factorsNucleotide exchange factorsGTPase-activating proteinsMyosin II activityActin-myosin contractionCytoskeletal dynamicsActin cytoskeletonCellular tensionExchange factorRho proteinsProtein TyrAdhesion dynamicsMorphogenetic processesCell rearAdhesion sizeCell frontIntegrin clusteringActin polymerizationRho activationMyosin IIDownstream signalingFeedback loopCell migrationComplex feedback loops
2008
Cell adhesion receptors in mechanotransduction
Schwartz MA, DeSimone DW. Cell adhesion receptors in mechanotransduction. Current Opinion In Cell Biology 2008, 20: 551-556. PMID: 18583124, PMCID: PMC2581799, DOI: 10.1016/j.ceb.2008.05.005.Peer-Reviewed Original ResearchConceptsAdhesion receptorsCell fate decisionsCadherin-mediated adhesionCell adhesion receptorsFate decisionsMorphogenetic movementsTissue-level responsesCultured cellsExtracellular matrixMechanotransductionLevel responseCellsCytoskeletonCadherinReceptorsOrganismsAdhesionIntegrinsPathwayMechanical stimulationIntracellularMechanismMechanical stressResponseCentral mechanisms
2006
Integrating Adhesion, Protrusion, and Contraction during Cell Migration
Schwartz MA, Horwitz AR. Integrating Adhesion, Protrusion, and Contraction during Cell Migration. Cell 2006, 125: 1223-1225. PMID: 16814706, DOI: 10.1016/j.cell.2006.06.015.Peer-Reviewed Original Research
2004
p21-activated Kinase Regulates Endothelial Permeability through Modulation of Contractility*
Stockton RA, Schaefer E, Schwartz MA. p21-activated Kinase Regulates Endothelial Permeability through Modulation of Contractility*. Journal Of Biological Chemistry 2004, 279: 46621-46630. PMID: 15333633, DOI: 10.1074/jbc.m408877200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBlotting, WesternCattleCell CommunicationCells, CulturedCytokinesCytoskeletonEndothelium, VascularEnzyme ActivationHumansInflammationIschemiaMicroscopy, FluorescenceMuscle ContractionMyosin Light ChainsP21-Activated KinasesPeptidesPhosphorylationProtein Serine-Threonine KinasesProtein TransportThrombinTime FactorsTransfectionUmbilical VeinsConceptsP21-activated kinaseClose cell-cell associationsEndothelial cell-cell junctionsCell-cell junctionsActin stress fibersCell-cell associationsSuitable drug targetsGrowth factorMyosin phosphorylationHuman umbilical vein endothelial cellsCentral regulatorStress fibersUmbilical vein endothelial cellsEndothelial cellsPAK activationDrug targetsVein endothelial cellsCell contractilityMultiple growth factorsParacellular poresEndothelial permeabilityPhosphorylationPathological processesPathological conditionsPotential roleIntegrins in Mechanotransduction*
Katsumi A, Orr AW, Tzima E, Schwartz MA. Integrins in Mechanotransduction*. Journal Of Biological Chemistry 2004, 279: 12001-12004. PMID: 14960578, DOI: 10.1074/jbc.r300038200.Peer-Reviewed Original Research
2003
Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells
Tzima E, Reader J, Irani-Tehrani M, Ewalt K, Schwartz M, Schimmel P. Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 14903-14907. PMID: 14630953, PMCID: PMC299850, DOI: 10.1073/pnas.2436330100.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acyl-tRNA SynthetasesAnimalsCattleCytoskeletonEndothelium, VascularGenetic VectorsHumansLuciferasesMicroscopy, FluorescenceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNeovascularization, PathologicNitric Oxide SynthaseProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsProto-Oncogene Proteins c-aktSignal TransductionStress, MechanicalTemperatureTime FactorsTranscription, GeneticConceptsT2-TrpRSStress-responsive gene expressionHuman tryptophanyl-tRNA synthetaseStress-responsive genesExtracellular signal-regulated kinase 1/2Growth factor stimulationHuman tRNA SynthetaseSignal-regulated kinase 1/2Natural splice variantProtein kinase BShear stress-responsive genesVascular endothelial growth factor (VEGF) stimulationTryptophanyl-tRNA synthetaseVascular homeostasisGrowth factor-induced angiogenesisVascular endothelial growth factor-induced angiogenesisCytoskeletal reorganizationProtein kinaseFactor stimulationAngiogenesis-related activitiesGene expressionKinase BKinase 1/2TRNA synthetaseEndothelial cell responses
2002
Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression
Tzima E, Del Pozo MA, Kiosses WB, Mohamed SA, Li S, Chien S, Schwartz MA. Activation of Rac1 by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression. The EMBO Journal 2002, 21: 6791-6800. PMID: 12486000, PMCID: PMC139108, DOI: 10.1093/emboj/cdf688.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCattleCell AdhesionCells, CulturedCytoskeletonDimerizationEnergy TransferEnzyme ActivationGene Expression RegulationGenes, DominantGreen Fluorescent ProteinsGTP PhosphohydrolasesIntercellular Adhesion Molecule-1LeukocytesLuciferasesLuminescent ProteinsMicroscopy, FluorescenceNF-kappa BPlasmidsProtein TransportRac GTP-Binding ProteinsRac1 GTP-Binding ProteinSpectrometry, FluorescenceStress, MechanicalTime FactorsTransfectionConceptsGene expressionFluorescence resonance energy transferSmall GTPase RacActivation of Rac1Endothelial cellsFocal adhesionsCytoskeletal organizationCytoskeletal reorganizationGTPase RacRac1 activationAdhesion receptorsResonance energy transferExtracellular matrixNuclear factor-kappaBNew integrinRac1Hemodynamic shear stressSubsequent expressionFactor-kappaBCell alignmentExpressionUnifying modelHemodynamic forcesCell adhesion molecule-1Cells
2001
Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration
Calderwood D, Huttenlocher A, Kiosses W, Rose D, Woodside D, Schwartz M, Ginsberg M. Increased filamin binding to β-integrin cytoplasmic domains inhibits cell migration. Nature Cell Biology 2001, 3: 1060-1068. PMID: 11781567, DOI: 10.1038/ncb1201-1060.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBinding SitesCell MovementCell PolarityCHO CellsContractile ProteinsCricetinaeCytoplasmCytoskeletonFibronectinsFilaminsFocal AdhesionsHumansIntegrin beta ChainsIntegrinsIsoleucineJurkat CellsMicrofilament ProteinsProtein Structure, TertiaryRecombinant Fusion ProteinsTalinValineConceptsFocal adhesion formationFilamin bindingCell migrationMembrane protrusionsMatrix assemblyIntegrin-dependent cell migrationFibronectin matrix assemblyAmino acid substitutionsInhibits cell migrationAnimal developmentActin cytoskeletonIntegrin tailsBiochemical signalsAdhesion receptorsFilaminCell polarizationTalinAcid substitutionsExtracellular matrixAdhesion formationTailBindingAssemblyMigrationSelective lossActivation of integrins in endothelial cells by fluid shear stress mediates Rho‐dependent cytoskeletal alignment
Tzima E, del Pozo M, Shattil S, Chien S, Schwartz M. Activation of integrins in endothelial cells by fluid shear stress mediates Rho‐dependent cytoskeletal alignment. The EMBO Journal 2001, 20: 4639-4647. PMID: 11532928, PMCID: PMC125600, DOI: 10.1093/emboj/20.17.4639.Peer-Reviewed Original ResearchAnimalsAortaCattleCells, CulturedCulture Media, Serum-FreeCytoskeletonEndothelium, VascularExtracellular Matrix ProteinsFibronectinsGreen Fluorescent ProteinsIntegrinsKineticsLuminescent ProteinsProtein ConformationReceptors, VitronectinRecombinant ProteinsRho GTP-Binding ProteinsStress, MechanicalTime FactorsTransfection
2000
The Molecular Adapter SLP-76 Relays Signals from Platelet Integrin αIIbβ3 to the Actin Cytoskeleton*
Obergfell A, Judd B, del Pozo M, Schwartz M, Koretzky G, Shattil S. The Molecular Adapter SLP-76 Relays Signals from Platelet Integrin αIIbβ3 to the Actin Cytoskeleton*. Journal Of Biological Chemistry 2000, 276: 5916-5923. PMID: 11113155, DOI: 10.1074/jbc.m010639200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsBlood PlateletsCell AdhesionCell Cycle ProteinsCHO CellsCricetinaeCytoskeletonEnzyme PrecursorsFibrinogenHumansIntracellular Signaling Peptides and ProteinsPhosphoproteinsPhosphorylationPlatelet Glycoprotein GPIIb-IIIa ComplexProtein BindingProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-vavPseudopodiaRac GTP-Binding ProteinsSignal TransductionSyk KinaseConceptsSLP-76SLAP-130Lamellipodia formationSLP-76 functionAdhesion-dependent activationCHO cell adhesionCell expression systemSLP-76 phosphorylationChinese hamster ovary cell expression systemSLP-76 expressionSyk tyrosine kinasePlatelet integrin αIIbβ3Sites of adhesionRac effectorPAK kinasesActin cytoskeletonAdherent CHO cellsExchange factorActin rearrangementCytoskeletal reorganizationActin reorganizationTyrosine phosphorylationExpression systemCell spreadingTyrosine kinaseFocal adhesion kinase suppresses Rho activity to promote focal adhesion turnover
Ren X, Kiosses W, Sieg D, Otey C, Schlaepfer D, Schwartz M. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. Journal Of Cell Science 2000, 113: 3673-3678. PMID: 11017882, DOI: 10.1242/jcs.113.20.3673.Peer-Reviewed Original Research
1999
Regulation of the small GTP‐binding protein Rho by cell adhesion and the cytoskeleton
Ren X, Kiosses W, Alexander Schwartz M. Regulation of the small GTP‐binding protein Rho by cell adhesion and the cytoskeleton. The EMBO Journal 1999, 18: 578-585. PMID: 9927417, PMCID: PMC1171150, DOI: 10.1093/emboj/18.3.578.Peer-Reviewed Original ResearchConceptsFocal adhesionsRho activationRho activityExtracellular matrixSmall GTPProtein RhoLysophosphatidic acidStress fibersCell adhesionRho-dependent mannerActin stress fibersHigh Rho activitySwiss 3T3 cellsNegative feedback loopAdherent cellsCytoskeletal structuresSoluble factorsCytochalasin DRhoGTPPresence of serumCellsActivationRegulationAdhesion