2024
Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis
Chanduri M, Kumar A, Weiss D, Emuna N, Barsukov I, Shi M, Tanaka K, Wang X, Datye A, Kanyo J, Collin F, Lam T, Schwarz U, Bai S, Nottoli T, Goult B, Humphrey J, Schwartz M. Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis. Science Advances 2024, 10: eadi6286. PMID: 39167642, PMCID: PMC11338229, DOI: 10.1126/sciadv.adi6286.Peer-Reviewed Original ResearchMeSH KeywordsActin-Related Protein 2-3 ComplexAnimalsAortaBiomechanical PhenomenaExtracellular MatrixHomeostasisHumansMechanotransduction, CellularMiceMutationProtein BindingTalinConceptsTissue mechanical homeostasisStiffness sensingExtracellular matrixTalin-1Mechanical homeostasisExtracellular matrix mechanicsIncreased cell spreadingCell spreadingTalinMutationsCellular sensingFibrillar collagenReduced axial stiffnessTissue mechanical propertiesMechanical propertiesAxial stiffnessCompliant substratesHomeostasisRupture pressureArp2/3ARPC5LStiffnessHomeostasis hypothesisResident cellsTissue stiffness
2023
TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity
Gallego-Paez L, Edwards W, Chanduri M, Guo Y, Koorman T, Lee C, Grexa N, Derksen P, Yan J, Schwartz M, Mauer J, Goult B. TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity. Journal Of Cell Biology 2023, 222: e202209010. PMID: 36880935, PMCID: PMC9997659, DOI: 10.1083/jcb.202209010.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingExonsHumansMechanotransduction, CellularNeoplasmsTalinConceptsExon 17bTerminal FERM domainVinculin bindingFERM domainSwitch domainAdhesion dynamicsCassette exonsSplicing analysisAdapter proteinTLN1Single isoformIsoform switchTalin-1Amino acidsFrame insertionExonsBiochemical analysisIsoformsProteinExon 17CytoskeletonGenesMechanotransductionDomainIntegrins
2022
Integrin Conformational Dynamics and Mechanotransduction
Kolasangiani R, Bidone T, Schwartz M. Integrin Conformational Dynamics and Mechanotransduction. Cells 2022, 11: 3584. PMID: 36429013, PMCID: PMC9688440, DOI: 10.3390/cells11223584.Peer-Reviewed Original ResearchConceptsCell-cell adhesionCell-extracellular matrixExtracellular ligandsIntegrin affinityConformational dynamicsIntegrin familyConformational statesConformational transitionTissue integrityCell functionCentral mediatorRemarkable convergenceMechanical forcesForce transmissionCytoskeletonMechanotransductionAdhesionFirm adhesionUnanswered questionsIntegrinsNew informationPathwayLigands
2021
Talin in mechanotransduction and mechanomemory at a glance
Goult BT, Brown NH, Schwartz MA. Talin in mechanotransduction and mechanomemory at a glance. Journal Of Cell Science 2021, 134: jcs258749. PMID: 34708856, PMCID: PMC8697387, DOI: 10.1242/jcs.258749.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesIntegrinsMechanotransduction, CellularProtein BindingSignal TransductionTalinConceptsHelical bundleHead domainC-terminal rod domainIntegrin conformational activationCytoskeletal linker proteinTerminal head domainExtracellular matrix proteinsCryptic binding sitesFlexible neck regionGlance articleAccompanying posterLinker proteinCytoplasmic tailConformational activationRod domainActin filamentsMatrix proteinsCell scienceTalinProteinBinding sitesDomain linksForce inducesDomainMechanotransductionEarly 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
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 recognitionResponseAutoinflammationLungInfectionMice
2018
Talin as a mechanosensitive signaling hub
Goult BT, Yan J, Schwartz MA. Talin as a mechanosensitive signaling hub. Journal Of Cell Biology 2018, 217: 3776-3784. PMID: 30254032, PMCID: PMC6219721, DOI: 10.1083/jcb.201808061.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsExtracellular MatrixHumansIntegrinsMechanotransduction, CellularProtein DomainsProtein Structure, SecondaryTalinConceptsSignaling hubsExtracellular matrixRod domainTalin rod domainIntegrin β subunitsDifferent protein interactionsLong rod domainSwitch-like behaviorActin cytoskeletonCytoplasmic domainCytoplasmic proteinsProtein interactionsHelical bundleGlobular head domainTalin functionTransmembrane receptorsHelix bundleΒ-subunitHead domainIntegrin familyTalinCell adhesionIndividual domainsRecent evidenceDomainLocal 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
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
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 HemorrhagicTalin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity
Kumar A, Ouyang M, Van den Dries K, McGhee EJ, Tanaka K, Anderson MD, Groisman A, Goult BT, Anderson KI, Schwartz MA. Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity. Journal Of Cell Biology 2016, 213: 371-383. PMID: 27161398, PMCID: PMC4862330, DOI: 10.1083/jcb.201510012.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsBinding SitesFluorescence Resonance Energy TransferFocal AdhesionsMechanotransduction, CellularMiceModels, BiologicalNIH 3T3 CellsTalinVinculinConceptsTalin tension sensorFar C-terminusIntegrin-dependent adhesionPeripheral adhesionsTension sensorFocal adhesionsCellular mechanosensingMechanosensitive structuresTalin functionC-terminusDistinct functionsRod domainStiffness sensingTalinVinculinActin filamentsABS3Site 2Soft substratesAdhesionForce transmissionMechanosensingNew lightTerminusEndothelial fluid shear stress sensing in vascular health and disease
Baeyens N, Bandyopadhyay C, Coon BG, Yun S, Schwartz MA. Endothelial fluid shear stress sensing in vascular health and disease. Journal Of Clinical Investigation 2016, 126: 821-828. PMID: 26928035, PMCID: PMC4767335, DOI: 10.1172/jci83083.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtherosclerosisBiomechanical PhenomenaEndothelium, VascularHumansMechanotransduction, CellularPlaque, AtheroscleroticVascular RemodelingConceptsNormal morphogenesisBiochemical signalsGene expressionSame pathwayFluid shear stressCell behaviorSpecialized mechanismsMorphogenesisPathwayPathological conditionsEndothelial cellsVascular physiologyVascular systemBasic mechanismsRecent advancesFlow signalingSignalingMechanismAdult lifePhysiologyExpressionSpider 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 ResearchMeSH KeywordsAnimalsBiomechanical PhenomenaEndothelial CellsHumansMechanotransduction, CellularModels, BiologicalStress, MechanicalVascular Remodeling
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-3ZO-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, CellularMechanotransduction of shear stress occurs through changes in VE-cadherin and PECAM-1 tension: Implications for cell migration
Conway DE, Schwartz MA. Mechanotransduction of shear stress occurs through changes in VE-cadherin and PECAM-1 tension: Implications for cell migration. Cell Adhesion & Migration 2014, 9: 335-339. PMID: 25482618, PMCID: PMC4955370, DOI: 10.4161/19336918.2014.968498.Peer-Reviewed Original ResearchDysfunctional Mechanosensing in Aneurysms
Humphrey JD, Milewicz DM, Tellides G, Schwartz MA. Dysfunctional Mechanosensing in Aneurysms. Science 2014, 344: 477-479. PMID: 24786066, PMCID: PMC4360903, DOI: 10.1126/science.1253026.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAorta, AbdominalAortic Aneurysm, AbdominalBlood PressureExtracellular MatrixHumansMechanotransduction, Cellular