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 ResearchConceptsTissue 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
2022
The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix
Herrera JA, Dingle L, Fernandez M, Venkateswaran RV, Blaikley JF, Lawless C, Schwartz MA. The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix. JCI Insight 2022, 7: e156115. PMID: 35852874, PMCID: PMC9462507, DOI: 10.1172/jci.insight.156115.Peer-Reviewed Original Research
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 stiffnessDeformationFibroblastsStiffnessCellsStretchForceExpressionTalin 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 evidenceDomainhMENA isoforms impact NSCLC patient outcome through fibronectin/β1 integrin axis
Di Modugno F, Spada S, Palermo B, Visca P, Iapicca P, Di Carlo A, Antoniani B, Sperduti I, Di Benedetto A, Terrenato I, Mottolese M, Gandolfi F, Facciolo F, Chen EI, Schwartz MA, Santoni A, Bissell MJ, Nisticò P. hMENA isoforms impact NSCLC patient outcome through fibronectin/β1 integrin axis. Oncogene 2018, 37: 5605-5617. PMID: 29907768, PMCID: PMC6193944, DOI: 10.1038/s41388-018-0364-3.Peer-Reviewed Original ResearchConceptsCell lung cancer patientsNSCLC patient outcomeFavorable clinical outcomeLung cancer patientsMechanism of actionClinical outcomesCancer patientsStromal fibronectinClinical managementTranscription factor 1Patient outcomesPatient riskΒ1 integrin expressionIntegrin axisNuclear expressionIntegrin expressionCell invasivenessCancer cellsFibronectin productionExtracellular matrix componentsFactor 1G-actin/F-actin ratioΒ1 integrin activationΒ1 integrin ligandsHMenaInhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis
Budatha M, Zhang J, Zhuang ZW, Yun S, Dahlman JE, Anderson DG, Schwartz MA. Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis. Journal Of The American Heart Association 2018, 7: e007501. PMID: 29382667, PMCID: PMC5850249, DOI: 10.1161/jaha.117.007501.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesAtherosclerosisCyclic Nucleotide Phosphodiesterases, Type 4Disease Models, AnimalExtracellular MatrixFibronectinsFibrosisGenetic Predisposition to DiseaseHindlimbInflammation MediatorsIntegrin alpha2Integrin alpha5IschemiaLeukocytesMaleMatrix MetalloproteinasesMice, Inbred C57BLMice, Knockout, ApoEMuscle, SkeletalNeovascularization, PhysiologicNF-kappa BPhenotypePlaque, AtheroscleroticSignal TransductionVascular RemodelingConceptsEndothelial inflammatory activationAtherosclerotic plaque sizeInflammatory activationPlaque stabilityVascular remodelingEndothelial NF-κB activationSmooth muscle cell contentPlaque sizeFemoral artery ligationMuscle cell contentTreatment of atherosclerosisInflammatory gene expressionPotential therapeutic targetFibrous cap thicknessNF-κB activationSmaller atherosclerotic plaquesArtery ligationAortic rootHindlimb ischemiaCompensatory remodelingAtherosclerotic plaquesTherapeutic targetLeukocyte contentMetalloproteinase expressionEndothelial basement membrane
2016
Interaction 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 bindingSignalingCellsFibronectinAtherosclerosisArteryForce regulated conformational change of integrin αVβ3
Chen Y, Lee H, Tong H, Schwartz M, Zhu C. Force regulated conformational change of integrin αVβ3. Matrix Biology 2016, 60: 70-85. PMID: 27423389, PMCID: PMC5237428, DOI: 10.1016/j.matbio.2016.07.002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomechanical PhenomenaBiotinylationCell AdhesionCell LineEndothelial CellsErythrocytesExtracellular MatrixFibronectinsGene ExpressionGlassHumansIntegrin alphaVbeta3KineticsLungMiceMolecular ProbesPoint MutationProtein BindingProtein ConformationSignal TransductionSingle Molecule ImagingConceptsConformational changesTransduce signalsSingle-molecule levelIntegrin functionBiomembrane force probeMolecular machinesPhysiological functionsCell adhesionCell surfaceExtracellular matrixPoint mutationsConformational transitionIntegrinsEssential roleTumor metastasisExtended conformationConformationDynamic equilibriumEctodomainMutationsForce probePhagocytosisMembraneAngiogenesisFunctionComparative 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
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, CellularDysfunctional 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
2013
Integrins 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 ResearchMeSH KeywordsActin CytoskeletonAnimalsCell AdhesionExtracellular MatrixHumansIntegrinsMechanotransduction, CellularConceptsMolecular mechanismsIntegrin-mediated adhesionImportant regulatory eventActin cytoskeletonRegulatory eventsExtracellular matrixNormal physiologyCell functionMajor insightsCentral roleCellsRecent advancesCytoskeletonEffect of forceMechanotransductionAdhesionIntegrinsPathwayPhysiologyMechanismRecent workDeconstructing 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 cellsActivationPathwayCellsSuper-Resolution Microscopy: A New Dimension in Focal Adhesions
Schwartz MA. Super-Resolution Microscopy: A New Dimension in Focal Adhesions. Current Biology 2011, 21: r115-r116. PMID: 21300274, DOI: 10.1016/j.cub.2010.12.025.Peer-Reviewed Original Research
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 forcesRemembrance of Dead Cells Past: Discovering That the Extracellular Matrix Is a Cell Survival Factor
Schwartz MA. Remembrance of Dead Cells Past: Discovering That the Extracellular Matrix Is a Cell Survival Factor. Molecular Biology Of The Cell 2010, 21: 499-500. PMID: 20150528, PMCID: PMC2820415, DOI: 10.1091/mbc.e09-07-0602.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell SurvivalExtracellular MatrixFemaleHistory, 20th CenturyHumansIntegrinsNeoplasmsPregnancySignal Transduction
2009
The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow
Hahn C, Orr AW, Sanders JM, Jhaveri KA, Schwartz MA. The Subendothelial Extracellular Matrix Modulates JNK Activation by Flow. Circulation Research 2009, 104: 995-1003. PMID: 19286608, PMCID: PMC2702158, DOI: 10.1161/circresaha.108.186486.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoproteins EAtherosclerosisBasement MembraneCattleCell Culture TechniquesCells, CulturedCollagenDisease Models, AnimalEndothelial CellsEnzyme ActivationExtracellular MatrixFibronectinsHemorheologyInflammationIntegrinsJNK Mitogen-Activated Protein KinasesMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase KinasesOscillometryP21-Activated KinasesPhosphorylationRegional Blood FlowStress, MechanicalCadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix Organization
Dzamba BJ, Jakab KR, Marsden M, Schwartz MA, DeSimone DW. Cadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix Organization. Developmental Cell 2009, 16: 421-432. PMID: 19289087, PMCID: PMC2682918, DOI: 10.1016/j.devcel.2009.01.008.Peer-Reviewed Original ResearchConceptsCadherin adhesionBlastocoel roofPlanar cell polarity signalingMatrix assemblyCell polarity signalingCell-cell adhesionFN fibril formationFN fibril assemblyPolarity signalingFocal adhesionsActin reorganizationXenopus embryosRegulatory pathwaysMyosin contractilityFibronectin matrixMatrix organizationSpatiotemporal localizationCultured cellsCell surfaceAnalogous roleFibril formationFibril assemblyFibrillar matrixMechanical tensionAssembly
2008
Integrin Agonists as Adjuvants in Chemotherapy for Melanoma
Schwartz MA, McRoberts K, Coyner M, Andarawewa KL, Frierson HF, Sanders JM, Swenson S, Markland F, Conaway MR, Theodorescu D. Integrin Agonists as Adjuvants in Chemotherapy for Melanoma. Clinical Cancer Research 2008, 14: 6193-6197. PMID: 18829498, DOI: 10.1158/1078-0432.ccr-08-1285.Peer-Reviewed Original ResearchConceptsMelanoma linesExtracellular matrixMetastatic melanomaM21 tumorsTherapeutic responseImmunodeficient miceTumor volumeChemotherapyClonal growth assaysTherapy resistanceTumor growthHuman melanomaChemotherapeutic efficacyMelanomaTumor cellsDrug 1Survival assaysM21 cellsM21 melanomaSmall nestsIntegrin agonistsIntegrin-dependent adhesionTumorsMiceSnake venom