The Experts below are selected from a list of 33318 Experts worldwide ranked by ideXlab platform
Hsinyao Tang - One of the best experts on this subject based on the ideXlab platform.
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mechanosensing by the lamina protects against nuclear rupture dna damage and cell cycle arrest
Developmental Cell, 2019Co-Authors: Manasvita Vashisth, Amal Abbas, Stephanie Majkut, Kenneth Vogel, Irena L Ivanovska, Jerome Irianto, Manorama Tewari, Elisia D Tichy, Foteini Mourkioti, Hsinyao TangAbstract:Summary Whether cell forces or extracellular matrix (ECM) can impact genome integrity is largely unclear. Here, acute perturbations (∼1 h) to actomyosin stress or ECM elasticity cause rapid and reversible changes in lamin-A, DNA damage, and cell cycle. The findings are especially relevant to organs such as the heart because DNA damage permanently arrests cardiomyocyte proliferation shortly after birth and thereby eliminates regeneration after injury including heart attack. Embryonic hearts, cardiac-differentiated iPS Cells (induced pluripotent stem Cells), and various nonmuscle cell types all show that actomyosin-driven nuclear rupture causes cytoplasmic mis-localization of DNA repair factors and excess DNA damage. Binucleation and micronuclei increase as telomeres shorten, which all favor cell-cycle arrest. Deficiencies in lamin-A and repair factors exacerbate these effects, but lamin-A-associated defects are rescued by repair factor overexpression and also by contractility modulators in clinical trials. Contractile Cells on stiff ECM normally exhibit low phosphorylation and slow degradation of lamin-A by matrix-metalloprotease-2 (MMP2), and inhibition of this lamin-A turnover and also actomyosin contractility are seen to minimize DNA damage. Lamin-A is thus stress stabilized to mechano-protect the genome.
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mechanosensing by the lamina protects against nuclear rupture dna damage and cell cycle arrest
bioRxiv, 2019Co-Authors: Manasvita Vashisth, Amal Abbas, Stephanie Majkut, Kenneth Vogel, Irena L Ivanovska, Jerome Irianto, Manorama Tewari, Elisia D Tichy, Foteini Mourkioti, Hsinyao TangAbstract:Summary Whether cell forces or extracellular matrix (ECM) can impact genome integrity is largely unclear. Here, acute perturbations (~1hr) to actomyosin stress or ECM elasticity cause rapid and reversible changes in lamin-A, DNA damage, and cell cycle. Embryonic hearts, differentiated iPS-Cells, and various nonmuscle cell types all show that actomyosin-driven nuclear rupture causes cytoplasmic mis-localization of DNA repair factors and excess DNA damage. Binucleation and micronuclei increase as telomeres shorten, which all favor cell cycle arrest. Deficiencies in lamin-A and repair factors exacerbate these effects, but lamin-A-associated defects are rescued by repair factor overexpression and by contractility modulators in clinical trials. Contractile Cells on stiff ECM normally exhibit low phosphorylation and slow degradation of lamin-A by matrix-metalloprotease-2 (MMP2), and inhibition of this lamin-A turnover and also actomyosin contractility is seen to minimize DNA damage. Lamin-A is thus stress-stabilized to mechano-protect the genome.
Surabhi Sonam - One of the best experts on this subject based on the ideXlab platform.
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investigating the nature of active forces in tissues reveals how Contractile Cells can form extensile monolayers
Nature Materials, 2021Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Gautham Hari Narayana Sankara Narayana, Surabhi SonamAbstract:Actomyosin machinery endows Cells with contractility at a single-cell level. However, within a monolayer, Cells can be Contractile or extensile based on the direction of pushing or pulling forces exerted by their neighbours or on the substrate. It has been shown that a monolayer of fibroblasts behaves as a Contractile system while epithelial or neural progentior monolayers behave as an extensile system. Through a combination of cell culture experiments and in silico modelling, we reveal the mechanism behind this switch in extensile to Contractile as the weakening of intercellular contacts. This switch promotes the build-up of tension at the cell-substrate interface through an increase in actin stress fibres and traction forces. This is accompanied by mechanotransductive changes in vinculin and YAP activation. We further show that Contractile and extensile differences in cell activity sort Cells in mixtures, uncovering a generic mechanism for pattern formation during cell competition, and morphogenesis.
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author correction investigating the nature of active forces in tissues reveals how Contractile Cells can form extensile monolayers
Nature Materials, 2021Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Gautham Hari Narayana Sankara Narayana, Surabhi SonamAbstract:In the version of this Article originally published, the captions for Extended Data Figs. 1, 2 and 3 were in the wrong order and did not correspond to their associated figures. The correct captions are listed below and the Article has been corrected accordingly. In addition, the cell line MCF7 was mistakenly written as ‘MCF7A’ in seven instances in the main text, Methods and Extended Data Fig. 4 caption, and as ‘MCF10A’ in one instance in the ‘Author contributions’ section; these errors have now been corrected.
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Nature of active forces in tissues: how Contractile Cells can form extensile monolayers
2020Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Gautham Hari Narayana Sankara Narayana, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Surabhi Sonam, Alpha YapAbstract:Actomyosin machinery endows Cells with contractility at a single cell level. However, at a tissue scale, Cells can show either Contractile or extensile behaviour based on the direction of pushing or pulling forces due to neighbour interactions or substrate interactions. Previous studies have shown that a monolayer of fibroblasts behaves as a Contractile system 1 while a monolayer of epithelial Cells 2,3 or neural crest Cells behaves as an extensile system. 4 How these two contradictory sources of force generation can coexist has remained unexplained. Through a combination of experiments using MDCK (Madin Darby Canine Kidney) Cells, and in-silico modeling, we uncover the mechanism behind this switch in behaviour of epithelial cell monolayers from extensile to Contractile as the weakening of intercellular contacts. We find that this switch in active behaviour also promotes the buildup of tension at the cell-substrate interface through an increase in actin stress fibers and higher traction forces. This in turn triggers a mechanotransductive response in vinculin translocation to focal adhesion sites and YAP (Yes-associated protein) transcription factor activation. Our studies also show that differences in extensility and contractility act to sort Cells, thus determining a general mechanism for mechanobiological pattern formation during cell competition, morphogenesis and cancer progression.
Amin Doostmohammadi - One of the best experts on this subject based on the ideXlab platform.
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investigating the nature of active forces in tissues reveals how Contractile Cells can form extensile monolayers
Nature Materials, 2021Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Gautham Hari Narayana Sankara Narayana, Surabhi SonamAbstract:Actomyosin machinery endows Cells with contractility at a single-cell level. However, within a monolayer, Cells can be Contractile or extensile based on the direction of pushing or pulling forces exerted by their neighbours or on the substrate. It has been shown that a monolayer of fibroblasts behaves as a Contractile system while epithelial or neural progentior monolayers behave as an extensile system. Through a combination of cell culture experiments and in silico modelling, we reveal the mechanism behind this switch in extensile to Contractile as the weakening of intercellular contacts. This switch promotes the build-up of tension at the cell-substrate interface through an increase in actin stress fibres and traction forces. This is accompanied by mechanotransductive changes in vinculin and YAP activation. We further show that Contractile and extensile differences in cell activity sort Cells in mixtures, uncovering a generic mechanism for pattern formation during cell competition, and morphogenesis.
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author correction investigating the nature of active forces in tissues reveals how Contractile Cells can form extensile monolayers
Nature Materials, 2021Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Gautham Hari Narayana Sankara Narayana, Surabhi SonamAbstract:In the version of this Article originally published, the captions for Extended Data Figs. 1, 2 and 3 were in the wrong order and did not correspond to their associated figures. The correct captions are listed below and the Article has been corrected accordingly. In addition, the cell line MCF7 was mistakenly written as ‘MCF7A’ in seven instances in the main text, Methods and Extended Data Fig. 4 caption, and as ‘MCF10A’ in one instance in the ‘Author contributions’ section; these errors have now been corrected.
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Nature of active forces in tissues: how Contractile Cells can form extensile monolayers
2020Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Gautham Hari Narayana Sankara Narayana, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Surabhi Sonam, Alpha YapAbstract:Actomyosin machinery endows Cells with contractility at a single cell level. However, at a tissue scale, Cells can show either Contractile or extensile behaviour based on the direction of pushing or pulling forces due to neighbour interactions or substrate interactions. Previous studies have shown that a monolayer of fibroblasts behaves as a Contractile system 1 while a monolayer of epithelial Cells 2,3 or neural crest Cells behaves as an extensile system. 4 How these two contradictory sources of force generation can coexist has remained unexplained. Through a combination of experiments using MDCK (Madin Darby Canine Kidney) Cells, and in-silico modeling, we uncover the mechanism behind this switch in behaviour of epithelial cell monolayers from extensile to Contractile as the weakening of intercellular contacts. We find that this switch in active behaviour also promotes the buildup of tension at the cell-substrate interface through an increase in actin stress fibers and higher traction forces. This in turn triggers a mechanotransductive response in vinculin translocation to focal adhesion sites and YAP (Yes-associated protein) transcription factor activation. Our studies also show that differences in extensility and contractility act to sort Cells, thus determining a general mechanism for mechanobiological pattern formation during cell competition, morphogenesis and cancer progression.
Manasvita Vashisth - One of the best experts on this subject based on the ideXlab platform.
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mechanosensing by the lamina protects against nuclear rupture dna damage and cell cycle arrest
Developmental Cell, 2019Co-Authors: Manasvita Vashisth, Amal Abbas, Stephanie Majkut, Kenneth Vogel, Irena L Ivanovska, Jerome Irianto, Manorama Tewari, Elisia D Tichy, Foteini Mourkioti, Hsinyao TangAbstract:Summary Whether cell forces or extracellular matrix (ECM) can impact genome integrity is largely unclear. Here, acute perturbations (∼1 h) to actomyosin stress or ECM elasticity cause rapid and reversible changes in lamin-A, DNA damage, and cell cycle. The findings are especially relevant to organs such as the heart because DNA damage permanently arrests cardiomyocyte proliferation shortly after birth and thereby eliminates regeneration after injury including heart attack. Embryonic hearts, cardiac-differentiated iPS Cells (induced pluripotent stem Cells), and various nonmuscle cell types all show that actomyosin-driven nuclear rupture causes cytoplasmic mis-localization of DNA repair factors and excess DNA damage. Binucleation and micronuclei increase as telomeres shorten, which all favor cell-cycle arrest. Deficiencies in lamin-A and repair factors exacerbate these effects, but lamin-A-associated defects are rescued by repair factor overexpression and also by contractility modulators in clinical trials. Contractile Cells on stiff ECM normally exhibit low phosphorylation and slow degradation of lamin-A by matrix-metalloprotease-2 (MMP2), and inhibition of this lamin-A turnover and also actomyosin contractility are seen to minimize DNA damage. Lamin-A is thus stress stabilized to mechano-protect the genome.
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mechanosensing by the lamina protects against nuclear rupture dna damage and cell cycle arrest
bioRxiv, 2019Co-Authors: Manasvita Vashisth, Amal Abbas, Stephanie Majkut, Kenneth Vogel, Irena L Ivanovska, Jerome Irianto, Manorama Tewari, Elisia D Tichy, Foteini Mourkioti, Hsinyao TangAbstract:Summary Whether cell forces or extracellular matrix (ECM) can impact genome integrity is largely unclear. Here, acute perturbations (~1hr) to actomyosin stress or ECM elasticity cause rapid and reversible changes in lamin-A, DNA damage, and cell cycle. Embryonic hearts, differentiated iPS-Cells, and various nonmuscle cell types all show that actomyosin-driven nuclear rupture causes cytoplasmic mis-localization of DNA repair factors and excess DNA damage. Binucleation and micronuclei increase as telomeres shorten, which all favor cell cycle arrest. Deficiencies in lamin-A and repair factors exacerbate these effects, but lamin-A-associated defects are rescued by repair factor overexpression and by contractility modulators in clinical trials. Contractile Cells on stiff ECM normally exhibit low phosphorylation and slow degradation of lamin-A by matrix-metalloprotease-2 (MMP2), and inhibition of this lamin-A turnover and also actomyosin contractility is seen to minimize DNA damage. Lamin-A is thus stress-stabilized to mechano-protect the genome.
Lakshmi Balasubramaniam - One of the best experts on this subject based on the ideXlab platform.
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investigating the nature of active forces in tissues reveals how Contractile Cells can form extensile monolayers
Nature Materials, 2021Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Gautham Hari Narayana Sankara Narayana, Surabhi SonamAbstract:Actomyosin machinery endows Cells with contractility at a single-cell level. However, within a monolayer, Cells can be Contractile or extensile based on the direction of pushing or pulling forces exerted by their neighbours or on the substrate. It has been shown that a monolayer of fibroblasts behaves as a Contractile system while epithelial or neural progentior monolayers behave as an extensile system. Through a combination of cell culture experiments and in silico modelling, we reveal the mechanism behind this switch in extensile to Contractile as the weakening of intercellular contacts. This switch promotes the build-up of tension at the cell-substrate interface through an increase in actin stress fibres and traction forces. This is accompanied by mechanotransductive changes in vinculin and YAP activation. We further show that Contractile and extensile differences in cell activity sort Cells in mixtures, uncovering a generic mechanism for pattern formation during cell competition, and morphogenesis.
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author correction investigating the nature of active forces in tissues reveals how Contractile Cells can form extensile monolayers
Nature Materials, 2021Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Gautham Hari Narayana Sankara Narayana, Surabhi SonamAbstract:In the version of this Article originally published, the captions for Extended Data Figs. 1, 2 and 3 were in the wrong order and did not correspond to their associated figures. The correct captions are listed below and the Article has been corrected accordingly. In addition, the cell line MCF7 was mistakenly written as ‘MCF7A’ in seven instances in the main text, Methods and Extended Data Fig. 4 caption, and as ‘MCF10A’ in one instance in the ‘Author contributions’ section; these errors have now been corrected.
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Nature of active forces in tissues: how Contractile Cells can form extensile monolayers
2020Co-Authors: Lakshmi Balasubramaniam, Amin Doostmohammadi, Thuan Beng Saw, Gautham Hari Narayana Sankara Narayana, Romain Mueller, Tien Dang, Minnah Thomas, Shafali Gupta, Surabhi Sonam, Alpha YapAbstract:Actomyosin machinery endows Cells with contractility at a single cell level. However, at a tissue scale, Cells can show either Contractile or extensile behaviour based on the direction of pushing or pulling forces due to neighbour interactions or substrate interactions. Previous studies have shown that a monolayer of fibroblasts behaves as a Contractile system 1 while a monolayer of epithelial Cells 2,3 or neural crest Cells behaves as an extensile system. 4 How these two contradictory sources of force generation can coexist has remained unexplained. Through a combination of experiments using MDCK (Madin Darby Canine Kidney) Cells, and in-silico modeling, we uncover the mechanism behind this switch in behaviour of epithelial cell monolayers from extensile to Contractile as the weakening of intercellular contacts. We find that this switch in active behaviour also promotes the buildup of tension at the cell-substrate interface through an increase in actin stress fibers and higher traction forces. This in turn triggers a mechanotransductive response in vinculin translocation to focal adhesion sites and YAP (Yes-associated protein) transcription factor activation. Our studies also show that differences in extensility and contractility act to sort Cells, thus determining a general mechanism for mechanobiological pattern formation during cell competition, morphogenesis and cancer progression.