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 stiffnessHemodynamics and Wall Mechanics of Vascular Graft Failure
Szafron J, Heng E, Boyd J, Humphrey J, Marsden A. Hemodynamics and Wall Mechanics of Vascular Graft Failure. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: 1065-1085. PMID: 38572650, PMCID: PMC11043008, DOI: 10.1161/atvbaha.123.318239.Peer-Reviewed Original ResearchConceptsVascular graftsTissue-engineered vascular graftsWall mechanicsSolid mechanicsVascular graft failureLoad magnitudeMechanobiological processesLoadMechanobiological stimuliMechanosensitive signaling pathwaysBiomechanical stateWallGraft failureBiomechanical loadingCongenital heart surgeryCoronary artery bypass graftingEnd-organ dysfunctionGraft materialArtery bypass graftingFeedback loopComputational tools
2017
mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice
Jiao Y, Li G, Li Q, Ali R, Qin L, Li W, Qyang Y, Greif DM, Geirsson A, Humphrey JD, Tellides G. mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice. Arteriosclerosis Thrombosis And Vascular Biology 2017, 37: 1657-1666. PMID: 28751568, PMCID: PMC5574180, DOI: 10.1161/atvbaha.117.309653.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesCell ProliferationCollagenElastinEverolimusFocal Adhesion Kinase 1Genetic Predisposition to DiseaseHumansImatinib MesylateMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Mechanotransduction, CellularMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesMuscle, Smooth, VascularPhenotypePhosphorylationProtein Kinase InhibitorsSirolimusTime FactorsTOR Serine-Threonine KinasesVascular StiffnessWilliams SyndromeConceptsElastin deficiencyCollagen accumulationArterial phenotypeNull miceGrowth factorSmooth muscle cell proliferationMuscle cell proliferationEarly postnatal deathInhibition of mTORAortic fibrosisAortic obstructionMedial thickeningAortic stiffeningNeonatal deathLuminal stenosisPharmacological blockadeAbsence of elastinThoracic aortaTherapeutic benefitJuvenile micePostnatal deathMTOR inhibitionAortaHeterozygous lossMice
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