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
2022
High Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells
Deng H, Schwartz MA. High Fluid Shear Stress Inhibits Cytokine‐Driven Smad2/3 Activation in Vascular Endothelial Cells. Journal Of The American Heart Association 2022, 11: e025337. PMID: 35861829, PMCID: PMC9707828, DOI: 10.1161/jaha.121.025337.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCytokinesEndothelial CellsEpithelial-Mesenchymal TransitionMiceSignal TransductionStress, MechanicalConceptsInflammatory cytokinesSmad2/3 activationEndothelial cellsNuclear translocationInflammatory cytokine treatmentGrowth factor betaVascular endothelial cellsQuantitative polymerase chain reactionSmad2/3 nuclear translocationTarget gene expressionBackground AtherosclerosisInflammatory mediatorsInflammatory pathwaysPolymerase chain reactionResult of inhibitionCytokine treatmentInhibits CytokineFactor betaMesenchymal transitionHigh fluid shear stressCytokinesEndMTGene expressionLaminar fluid shear stressFluid shear stressA mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells
Coon BG, Timalsina S, Astone M, Zhuang ZW, Fang J, Han J, Themen J, Chung M, Yang-Klingler YJ, Jain M, Hirschi KK, Yamamato A, Trudeau LE, Santoro M, Schwartz MA. A mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells. Journal Of Cell Biology 2022, 221: e202109144. PMID: 35695893, PMCID: PMC9198948, DOI: 10.1083/jcb.202109144.Peer-Reviewed Original ResearchConceptsLaminar shear stressAnti-inflammatory transcription factorHigh laminar shear stressKruppel-like factor 2Vascular endothelial cellsSubsequent mechanistic investigationsArterial lesionsVascular inflammationDisturbed blood flowMyocardial infarctionVascular diseaseVascular remodelingBlood flowKLF2 expressionWhole-genome CRISPREndothelial cellsMajor causeBiomechanical factorsFactor 2Mitochondrial calciumMitochondrial metabolismKLF2InductionMetabolismMitochondrial pathwayMicroRNAs in Mechanical Homeostasis
Herrera JA, Schwartz MA. MicroRNAs in Mechanical Homeostasis. Cold Spring Harbor Perspectives In Medicine 2022, 12: a041220. PMID: 35379658, PMCID: PMC9380736, DOI: 10.1101/cshperspect.a041220.Peer-Reviewed Original Research
2021
Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling
Deng H, Min E, Baeyens N, Coon BG, Hu R, Zhuang ZW, Chen M, Huang B, Afolabi T, Zarkada G, Acheampong A, McEntee K, Eichmann A, Liu F, Su B, Simons M, Schwartz MA. Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2105339118. PMID: 34504019, PMCID: PMC8449390, DOI: 10.1073/pnas.2105339118.Peer-Reviewed Original ResearchConceptsLow fluid shear stressFluid shear stressNuclear translocationSmad linker regionTransmembrane protein Neuropilin-1Target gene expressionCyclin-dependent kinasesBone morphogenetic proteinEC-specific deletionSmad2/3 nuclear translocationNuclear localizationHigh fluid shear stressLinker regionMorphogenetic proteinsGene expressionRegulatory mechanismsActivation of Smad2/3Receptor ALK5Smad2/3 phosphorylationTranslocationCell sensingEndothelial cell (EC) sensingPhosphorylationALK5Smad2/3Early 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 questionsDevelopmental origins of mechanical homeostasis in the aorta
Murtada S, Kawamura Y, Li G, Schwartz MA, Tellides G, Humphrey JD. Developmental origins of mechanical homeostasis in the aorta. Developmental Dynamics 2021, 250: 629-639. PMID: 33341996, PMCID: PMC8089041, DOI: 10.1002/dvdy.283.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, BiologicalAnimalsAorta, ThoracicHomeostasisMaleMice, Inbred C57BLStress, MechanicalConceptsPostnatal days P2Intramural cellsSmooth muscle contractilityLate prenatal periodBlood pressureDays P2Muscle contractilityAortic structureMurine aortaPrenatal periodEndothelial cellsAortaPathological conditionsAortic developmentDeposition of matrixDevelopmental originsMatrix depositionHomeostasisHomeostatic stateCellsIntramural stressPressure-induced mechanical stressFlow-induced shear stressMechanical loadingContractility
2019
Filamin A mediates isotropic distribution of applied force across the actin network
Kumar A, Shutova MS, Tanaka K, Iwamoto DV, Calderwood DA, Svitkina TM, Schwartz MA. Filamin A mediates isotropic distribution of applied force across the actin network. Journal Of Cell Biology 2019, 218: 2481-2491. PMID: 31315944, PMCID: PMC6683746, DOI: 10.1083/jcb.201901086.Peer-Reviewed Original ResearchConceptsTalin tension sensorStress fibersActin networkFilamin ACortical actin networkCortical actin filamentsIntegrin-mediated adhesionActin cytoskeletonFocal adhesionsCortical actinFLNA knockdownActin filamentsTalinKnockdownCell sensingDirection of stretchTension sensorPhysiology of muscleUniaxial stretchForce transmissionCytoskeletonStrainsStretchAdhesionReexpressionTranslocating transcription factors in fluid shear stress-mediated vascular remodeling and disease
Min E, Schwartz MA. Translocating transcription factors in fluid shear stress-mediated vascular remodeling and disease. Experimental Cell Research 2019, 376: 92-97. PMID: 30633880, PMCID: PMC8211025, DOI: 10.1016/j.yexcr.2019.01.005.Peer-Reviewed Original Research
2017
Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification
Fang JS, Coon BG, Gillis N, Chen Z, Qiu J, Chittenden TW, Burt JM, Schwartz MA, Hirschi KK. Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification. Nature Communications 2017, 8: 2149. PMID: 29247167, PMCID: PMC5732288, DOI: 10.1038/s41467-017-01742-7.Peer-Reviewed Original ResearchConceptsEndothelial cell cycle arrestArterial gene expressionCell cycle arrestArterial specificationGene expressionCycle arrestArterial-venous specificationCell cycle inhibitor CDKN1BEndothelial cell cycleCell cycle inhibitionEmbryonic developmentBlood vessel formationP27 axisFunctional vascular networkCell cycleGrowth controlSpecialized phenotypeFluid shear stressCycle inhibitionVessel formationGrowth inhibitionTissue repairMechanochemical pathwayEndothelial cellsVascular regenerationVE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN
Conway DE, Coon BG, Budatha M, Arsenovic PT, Orsenigo F, Wessel F, Zhang J, Zhuang Z, Dejana E, Vestweber D, Schwartz MA. VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Current Biology 2017, 27: 2219-2225.e5. PMID: 28712573, PMCID: PMC5667920, DOI: 10.1016/j.cub.2017.06.020.Peer-Reviewed Original ResearchConceptsSrc family kinasesProtein LGNCytoplasmic tyrosinesVE-cadherinVascular endothelial growth factor receptorVE-cadherin functionJunctional complexesRespective cytoplasmic domainsBlood vessel developmentVE-cadherin phosphorylationTransduce forcesTransduce signalsCytoplasmic domainFamily kinasesBlood vessel remodelingGrowth factor receptorVEGFR activationPECAM-1Stress responseComplex consistingFluid shear stressVessel developmentFlow-dependent vascular remodelingSpecific poolPhosphorylation
2016
Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia
Baeyens N, Larrivée B, Ola R, Hayward-Piatkowskyi B, Dubrac A, Huang B, Ross TD, Coon BG, Min E, Tsarfati M, Tong H, Eichmann A, Schwartz MA. Defective fluid shear stress mechanotransduction mediates hereditary hemorrhagic telangiectasia. Journal Of Cell Biology 2016, 214: 807-816. PMID: 27646277, PMCID: PMC5037412, DOI: 10.1083/jcb.201603106.Peer-Reviewed Original ResearchActivin Receptors, Type IIArteriovenous MalformationsArteriovenous Shunt, SurgicalBone Morphogenetic ProteinsCell ProliferationEndoglinEndothelial CellsGene DeletionHEK293 CellsHemorheologyHuman Umbilical Vein Endothelial CellsHumansMechanotransduction, CellularPericytesRegional Blood FlowRetinaSignal TransductionSolubilityStress, MechanicalTelangiectasia, Hereditary HemorrhagicSpider Silk Peptide Is a Compact, Linear Nanospring Ideal for Intracellular Tension Sensing
Brenner MD, Zhou R, Conway DE, Lanzano L, Gratton E, Schwartz MA, Ha T. Spider Silk Peptide Is a Compact, Linear Nanospring Ideal for Intracellular Tension Sensing. Nano Letters 2016, 16: 2096-2102. PMID: 26824190, PMCID: PMC4851340, DOI: 10.1021/acs.nanolett.6b00305.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsElasticityFluorescence Resonance Energy TransferMechanotransduction, CellularPeptidesSilkSpidersStress, MechanicalConceptsSingle-molecule fluorescence-force spectroscopyFluorescence-force spectroscopyFluorescence resonance energy transferResonance energy transferRodlike structureSensor constructsShort peptidesIndividual chainsAccessible forcesEnergy transferSilk peptideCell imagingSpider silk proteinsBiological systemsRemarkable elasticitySilk proteinsFRETPN.PeptidesSpider silkPolymersSpectroscopyRecent developmentsForce sensitivityWide rangeBiomechanics of vascular mechanosensation and remodeling
Baeyens N, Schwartz MA. Biomechanics of vascular mechanosensation and remodeling. Molecular Biology Of The Cell 2016, 27: 7-11. PMID: 26715421, PMCID: PMC4694763, DOI: 10.1091/mbc.e14-11-1522.Peer-Reviewed Original Research
2015
Role of Mechanotransduction in Vascular Biology
Humphrey JD, Schwartz MA, Tellides G, Milewicz DM. Role of Mechanotransduction in Vascular Biology. Circulation Research 2015, 116: 1448-1461. PMID: 25858068, PMCID: PMC4420625, DOI: 10.1161/circresaha.114.304936.Peer-Reviewed Original ResearchConceptsExtracellular matrixRole of mechanotransductionExtracellular matrix constituentsActomyosin filamentsMembrane receptorsDysfunctional mechanosensingVascular biologyAortic aneurysmNew therapeutic strategiesContractile proteinsThoracic aortic aneurysmIntramural cellsCellsMechanobiological processesMatrix constituentsAcute dissectionAortic cellsAortic diseaseMechanosensingTherapeutic strategiesHemodynamic loadGenesProgressive enlargementReceptorsMechanoregulationIntramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex
Coon BG, Baeyens N, Han J, Budatha M, Ross TD, Fang JS, Yun S, Thomas JL, Schwartz MA. Intramembrane binding of VE-cadherin to VEGFR2 and VEGFR3 assembles the endothelial mechanosensory complex. Journal Of Cell Biology 2015, 208: 975-986. PMID: 25800053, PMCID: PMC4384728, DOI: 10.1083/jcb.201408103.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCadherinsCell MovementCells, CulturedEndothelium, VascularHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansMechanotransduction, CellularMiceMice, Inbred C57BLNeovascularization, PhysiologicPlaque, AtheroscleroticPlatelet Endothelial Cell Adhesion Molecule-1Protein Structure, TertiaryRNA InterferenceRNA, Small InterferingStress, MechanicalStress, PhysiologicalVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3
2014
Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling
Baeyens N, Mulligan-Kehoe MJ, Corti F, Simon DD, Ross TD, Rhodes JM, Wang TZ, Mejean CO, Simons M, Humphrey J, Schwartz MA. Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 17308-17313. PMID: 25404299, PMCID: PMC4260558, DOI: 10.1073/pnas.1413725111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisBlotting, WesternCells, CulturedEndothelial CellsFemaleHuman Umbilical Vein Endothelial CellsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalNF-kappa BReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionStress, MechanicalSyndecan-4Vascular Endothelial Growth Factor Receptor-2ConceptsHuman umbilical vein endothelial cellsNF-κBProinflammatory NF-κBAtherosclerotic plaque burdenKruppel-like factor 2Umbilical vein endothelial cellsVEGF receptor 2Appearance of plaquesVein endothelial cellsHypercholesterolemic micePlaque burdenAntiinflammatory pathwayThoracic aortaReceptor 2Endothelial cellsEndothelial alignmentFlow correlatesCausal roleAtherosclerosisFactor 2MiceCyclic stretchLocalization correlatesActivationSyndecan-4
2013
Endothelial Cell Sensing of Flow Direction
Wang C, Baker BM, Chen CS, Schwartz MA. Endothelial Cell Sensing of Flow Direction. Arteriosclerosis Thrombosis And Vascular Biology 2013, 33: 2130-2136. PMID: 23814115, PMCID: PMC3812824, DOI: 10.1161/atvbaha.113.301826.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsAtherosclerosisCattleCell Culture TechniquesCell ShapeCells, CulturedEndothelial CellsEnzyme ActivationHemodynamicsInflammationMechanotransduction, CellularNF-kappa BNitric OxideNitric Oxide Synthase Type IIIOscillometryPhosphorylationProto-Oncogene Proteins c-aktReactive Oxygen SpeciesRegional Blood FlowStress, MechanicalTime FactorsConceptsEndothelial cellsEndothelial nitric oxide synthaseEndothelial nitric oxide synthase pathwayNitric oxide synthase pathwayNitric oxide synthaseOxide synthase pathwayAtherosclerosis-prone regionsInflammatory activationInflammatory effectsOxide synthaseEndothelial cell responsesCell responsesReactive oxygen productionDisturbed flowNitric oxideNuclear factorSimilar effectsActivationCellsSynthase pathwayInability of cellsFluid 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 remodelingFlow-dependent cellular mechanotransduction in atherosclerosis
Conway DE, Schwartz MA. Flow-dependent cellular mechanotransduction in atherosclerosis. Journal Of Cell Science 2013, 126: 5101-5109. PMID: 24190880, PMCID: PMC3828588, DOI: 10.1242/jcs.138313.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisDisease ProgressionEndothelium, VascularHumansHypertensionMechanotransduction, CellularRisk FactorsStress, Mechanical