2021
Integrin-based mechanosensing through conformational deformation
Driscoll TP, Bidone TC, Ahn SJ, Yu A, Groisman A, Voth GA, Schwartz MA. Integrin-based mechanosensing through conformational deformation. Biophysical Journal 2021, 120: 4349-4359. PMID: 34509509, PMCID: PMC8553792, DOI: 10.1016/j.bpj.2021.09.010.Peer-Reviewed Original ResearchConceptsCellular mechanosensingFocal adhesion kinase activationIntegrin conformational activationLarge-scale conformational transitionsWild-type integrinIntegrin mutantsEmbryonic developmentConformational activationCellular stiffnessHigh-affinity stateKinase activationSubstrate stiffnessBiological processesIntegrin activationCell spreadingMutantsIntegrin conformationTraction stressConformational deformationConformational transitionIntegrinsMechanosensingSoluble ligandsAffinity stateMolecular-level information
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 regenerationLive 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 vesselsExpressionVangl2RemodelingCellsMorphogenesis
2015
Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization
Dubrac A, Genet G, Ola R, Zhang F, Pibouin-Fragner L, Han J, Zhang J, Thomas JL, Chedotal A, Schwartz MA, Eichmann A. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization. Circulation 2015, 133: 409-421. PMID: 26659946, PMCID: PMC4729599, DOI: 10.1161/circulationaha.115.017537.Peer-Reviewed Original ResearchConceptsFront-rear polaritySprouting angiogenesisSignal integration mechanismImportant drug targetsNck adaptorsCytoskeletal dynamicsEndothelial cell migrationEmbryonic developmentAngiogenesis defectsPAK2 activationVessel sproutsNumber of diseasesBlood vessel growthDrug targetsCell migrationPostnatal retinaAngiogenic growthNckNck1AdaptorVessel growthKey processesEndothelial cellsPathological ocular neovascularizationInhibits neovascularization
2011
Dynamic molecular processes mediate cellular mechanotransduction
Hoffman BD, Grashoff C, Schwartz MA. Dynamic molecular processes mediate cellular mechanotransduction. Nature 2011, 475: 316-323. PMID: 21776077, PMCID: PMC6449687, DOI: 10.1038/nature10316.Peer-Reviewed Original ResearchConceptsCell adhesion complexesDistinct signaling pathwaysTransduction of forceDynamic molecular processesEmbryonic developmentCellular mechanotransductionPlasma membraneBiochemical signalsAdult physiologySignaling pathwaysCellular responsesSubcellular structuresMolecular processesNumerous diseasesMechanical forcesMuscular dystrophyCytoskeletonTransductionMechanotransductionPathwayPhysiologyDisassemblyRecent workMembraneAssembly