2024
Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities
Stroope C, Nettersheim F, Coon B, Finney A, Schwartz M, Ley K, Rom O, Yurdagul A. Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities. Nature Metabolism 2024, 6: 617-638. PMID: 38532071, PMCID: PMC11055680, DOI: 10.1038/s42255-024-01015-w.Peer-Reviewed Original ResearchDysregulated cellular metabolismAtherosclerotic cardiovascular diseaseLesional cellsAtherosclerosis progressionCardiovascular diseaseDysregulation of cellular metabolismVascular smooth muscle cellsProgression of atherosclerotic cardiovascular diseaseSmooth muscle cellsCellular metabolismT cellsMetabolic alterationsMuscle cellsMetabolic dysregulationCardiovascular therapeuticsTherapeutic opportunitiesEndothelial cellsTherapeutic targetMetabolic cross-talkAtherosclerosisCellsDiseaseDysregulationCross-talkMetabolism
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 ResearchConceptsFluid 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 ResearchConceptsPostnatal 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
Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity
Solis AG, Bielecki P, Steach HR, Sharma L, Harman CCD, Yun S, de Zoete MR, Warnock JN, To SDF, York AG, Mack M, Schwartz MA, Dela Cruz CS, Palm NW, Jackson R, Flavell RA. Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity. Nature 2019, 573: 69-74. PMID: 31435009, PMCID: PMC6939392, DOI: 10.1038/s41586-019-1485-8.Peer-Reviewed Original ResearchConceptsInnate immune cellsImmune cellsInflammatory responseInnate immune systemCyclical hydrostatic pressurePulmonary inflammationImmune responseImmune systemInnate immunityBacterial infectionsIon channel Piezo1InflammationPhysiological fluctuationsImmunityPhysiological roleLocal microenvironmentCellsPiezo1Direct recognitionResponseAutoinflammationLungInfectionMiceMKL1-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
Vinculin and the mechanical response of adherent fibroblasts to matrix deformation
Rosowski KA, Boltyanskiy R, Xiang Y, Van den Dries K, Schwartz MA, Dufresne ER. Vinculin and the mechanical response of adherent fibroblasts to matrix deformation. Scientific Reports 2018, 8: 17967. PMID: 30568231, PMCID: PMC6299284, DOI: 10.1038/s41598-018-36272-9.Peer-Reviewed Original ResearchConceptsFocal adhesion protein vinculinAdhesion protein vinculinExtracellular matrix stiffnessIntegrin-mediated adhesionTraction forceProtein vinculinMechanical cuesCellular forcesMatrix stiffnessAdherent fibroblastsECM deformationMouse fibroblastsTraction stressMatrix deformationMechanical responseVinculinMechanical energyApparent stiffnessDeformationFibroblastsStiffnessCellsStretchForceExpression
2017
Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish
Lagendijk AK, Gomez GA, Baek S, Hesselson D, Hughes WE, Paterson S, Conway DE, Belting HG, Affolter M, Smith KA, Schwartz MA, Yap AS, Hogan BM. Live imaging molecular changes in junctional tension upon VE-cadherin in zebrafish. Nature Communications 2017, 8: 1402. PMID: 29123087, PMCID: PMC5680264, DOI: 10.1038/s41467-017-01325-6.Peer-Reviewed Original ResearchConceptsVE-cadherinEndothelial cell-cell junctionsCell-cell junctionsActo-myosin cytoskeletonTension sensorActo-myosin contractilityJunctional tensionEmbryonic developmentDiverse rolesVascular developmentLive zebrafishChemical perturbationsFRET measurementsZebrafishAdjacent cellsMolecular changesEndothelial cellsCellsBiosensor approachCytoskeletonHomeostasisLocalizationVivoTensile changesMatures
2016
Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development
Wang Y, Baeyens N, Corti F, Tanaka K, Fang JS, Zhang J, Jin Y, Coon B, Hirschi KK, Schwartz MA, Simons M. Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development. Development 2016, 143: 4441-4451. PMID: 27789626, PMCID: PMC5201046, DOI: 10.1242/dev.140129.Peer-Reviewed Original ResearchConceptsLymphatic endothelial cellsPlanar cell polarity protein Vangl2Lymphatic vessel remodelingMouse embryonic developmentHuman lymphatic endothelial cellsVangl2 overexpressionVangl2 expressionEmbryonic developmentValve morphogenesisEndothelial cellsVasculature developmentSyndecan-4Lymphatic vasculatureFluid shear stressSDC4Double knockout miceMice resultsHigh expressionVessel remodelingLymphatic vesselsExpressionVangl2RemodelingCellsMorphogenesisInteraction between integrin α5 and PDE4D regulates endothelial inflammatory signalling
Yun S, Budatha M, Dahlman JE, Coon BG, Cameron RT, Langer R, Anderson DG, Baillie G, Schwartz MA. Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling. Nature Cell Biology 2016, 18: 1043-1053. PMID: 27595237, PMCID: PMC5301150, DOI: 10.1038/ncb3405.Peer-Reviewed Original ResearchConceptsInflammatory signalingIntegrin α5Enhanced phosphodiesterase activityExtracellular matrix remodellingModulates inflammationTherapeutic targetInflammationProstacyclin secretionLipid metabolismEndothelial cellsMatrix remodellingVivo knockdownECM remodellingBasement membraneIntegrin α2Phosphodiesterase activityMolecular mechanismsRemodellingΑ5Direct bindingSignalingCellsFibronectinAtherosclerosisArteryComparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine
Balestrini JL, Gard AL, Gerhold KA, Wilcox EC, Liu A, Schwan J, Le AV, Baevova P, Dimitrievska S, Zhao L, Sundaram S, Sun H, Rittié L, Dyal R, Broekelmann TJ, Mecham RP, Schwartz MA, Niklason LE, White ES. Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine. Biomaterials 2016, 102: 220-230. PMID: 27344365, PMCID: PMC4939101, DOI: 10.1016/j.biomaterials.2016.06.025.Peer-Reviewed Original ResearchConceptsHuman endothelial cellsCell-matrix interactionsLung regenerationEndothelial cellsKey matrix proteinsComparative biologyCell adhesion moleculeMatrix proteinsLung extracellular matrixCell healthExtracellular matrixResidual DNASpecies mismatchRat lung scaffoldsRegenerative medicineAdhesion moleculesLung scaffoldsPrimate tissuesCellsVascular cell adhesion moleculeLung engineeringLung matrixLess expressionPulmonary cellsProfound effect
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 enlargementReceptorsMechanoregulation
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 Research
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 cellsIntegrins in mechanotransduction
Ross TD, Coon BG, Yun S, Baeyens N, Tanaka K, Ouyang M, Schwartz MA. Integrins in mechanotransduction. Current Opinion In Cell Biology 2013, 25: 613-618. PMID: 23797029, PMCID: PMC3757118, DOI: 10.1016/j.ceb.2013.05.006.Peer-Reviewed Original ResearchConceptsMolecular mechanismsIntegrin-mediated adhesionImportant regulatory eventActin cytoskeletonRegulatory eventsExtracellular matrixNormal physiologyCell functionMajor insightsCentral roleCellsRecent advancesCytoskeletonEffect of forceMechanotransductionAdhesionIntegrinsPathwayPhysiologyMechanismRecent workN-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways
Ouyang M, Lu S, Kim T, Chen CE, Seong J, Leckband DE, Wang F, Reynolds AB, Schwartz MA, Wang Y. N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways. Nature Communications 2013, 4: 1589. PMID: 23481397, PMCID: PMC3602931, DOI: 10.1038/ncomms2560.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsBeta CateninCadherinsCateninsCell PolarityChickensCHO CellsCricetinaeDelta CateninEmbryo, MammalianFibroblastsFluorescent DyesIntegrinsIntercellular JunctionsMiceModels, BiologicalPhosphatidylinositol 3-KinasesProtein BindingRac GTP-Binding ProteinsRatsRecombinant Fusion ProteinsRNA, Small InterferingSignal TransductionConceptsMyosin II light chainRac activityActin filamentsSmall GTPase RacΒ-catenin-dependent signaling pathwaysHigher phosphoinositidesCellular functionsGTPase RacDistinct effectorsMolecular signalsSignaling pathwaysMolecular activityLight chainNeighbouring cellsN-cadherinPhosphoinositideIntercellular junctionsIntegrin α5RacCellsComplexesFilamentsP120ctnSpatial distributionEffectorsDeconstructing Dimensionality
Schwartz MA, Chen CS. Deconstructing Dimensionality. Science 2013, 339: 402-404. PMID: 23349278, DOI: 10.1126/science.1233814.Peer-Reviewed Original ResearchConceptsStem cell nicheVivo cellular behaviorTwo-dimensional cultureCell nicheVivo functionGene expressionExtracellular matrix gelCellular behaviorTissue culture plasticCell behaviorDifferentiated functionsCell processesCulture plasticThree-dimensional environmentMatrix gelCellsTissue engineersMorphogenesisNicheBiologistsMajor advancesExpressionFunctionOnly minimal changesMaintenance
2011
JNK2 Promotes Endothelial Cell Alignment under Flow
Hahn C, Wang C, Orr AW, Coon BG, Schwartz MA. JNK2 Promotes Endothelial Cell Alignment under Flow. PLOS ONE 2011, 6: e24338. PMID: 21909388, PMCID: PMC3164210, DOI: 10.1371/journal.pone.0024338.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinase c-Jun N-terminal kinaseProtein kinase c-Jun N-terminal kinaseC-Jun N-terminal kinaseActin stress fibersN-terminal kinaseFocal adhesionsBasement membrane proteinsMembrane proteinsLaminar shear stressStress fibersGene expressionJNK activityIntegrin activationJNK2 activationEndothelial cell alignmentJNK activationActivated JNKExtracellular matrixInflammatory gene expressionCell alignmentUnexpected connectionEndothelial cellsActivationPathwayCells
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 forcesMeasuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics
Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 2010, 466: 263-266. PMID: 20613844, PMCID: PMC2901888, DOI: 10.1038/nature09198.Peer-Reviewed Original ResearchConceptsFocal adhesionsFocal adhesion dynamicsMembrane cytoskeletal proteinsAdhesion dynamicsCell adhesion moleculeRegulatory mechanismsSpecific proteinsActin filamentsCell adhesionVinculinProteinMechanical tensionMechanical forcesRegulationPhysical forcesMolecular forcesAdhesionCellsVivoMechanotransductionPhysiologyNew biosensorFilamentsAbilityMigration