Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate
Nuclear rupture has long been associated with deficits or defects in lamins, with recent results also indicating a role for actomyosin stress, but key physical determinants of rupture remain unclear. Here, lamin-B filaments stably interact with the nuclear membrane at sites of low Gaussian curvature...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-12-01
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| Series: | Nucleus |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19491034.2022.2045726 |
| _version_ | 1828230654809079808 |
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| author | Charlotte R. Pfeifer Michael P. Tobin Sangkyun Cho Manasvita Vashisth Lawrence J. Dooling Lizeth Lopez Vazquez Emma G. Ricci-De Lucca Keiann T. Simon Dennis E. Discher |
| author_facet | Charlotte R. Pfeifer Michael P. Tobin Sangkyun Cho Manasvita Vashisth Lawrence J. Dooling Lizeth Lopez Vazquez Emma G. Ricci-De Lucca Keiann T. Simon Dennis E. Discher |
| author_sort | Charlotte R. Pfeifer |
| collection | DOAJ |
| description | Nuclear rupture has long been associated with deficits or defects in lamins, with recent results also indicating a role for actomyosin stress, but key physical determinants of rupture remain unclear. Here, lamin-B filaments stably interact with the nuclear membrane at sites of low Gaussian curvature yet dilute at high curvature to favor rupture, whereas lamin-A depletion requires high strain-rates. Live-cell imaging of lamin-B1 gene-edited cancer cells is complemented by fixed-cell imaging of rupture in: iPS-derived progeria patients cells, cells within beating chick embryo hearts, and cancer cells with multi-site rupture after migration through small pores. Data fit a model of stiff filaments that detach from a curved surface.Rupture is modestly suppressed by inhibiting myosin-II and by hypotonic stress, which slow the strain-rates. Lamin-A dilution and rupture probability indeed increase above a threshold rate of nuclear pulling. Curvature-sensing mechanisms of proteins at plasma membranes, including Piezo1, might thus apply at nuclear membranes.Summary statement: High nuclear curvature drives lamina dilution and nuclear envelope rupture even when myosin stress is inhibited. Stiff filaments generally dilute from sites of high Gaussian curvature, providing mathematical fits of experiments. |
| first_indexed | 2024-04-12T18:52:46Z |
| format | Article |
| id | doaj.art-24f2d772cf1546849c968f505a41ab11 |
| institution | Directory Open Access Journal |
| issn | 1949-1034 1949-1042 |
| language | English |
| last_indexed | 2024-04-12T18:52:46Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Nucleus |
| spelling | doaj.art-24f2d772cf1546849c968f505a41ab112022-12-22T03:20:26ZengTaylor & Francis GroupNucleus1949-10341949-10422022-12-0113112914310.1080/19491034.2022.2045726Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rateCharlotte R. Pfeifer0Michael P. Tobin1Sangkyun Cho2Manasvita Vashisth3Lawrence J. Dooling4Lizeth Lopez Vazquez5Emma G. Ricci-De Lucca6Keiann T. Simon7Dennis E. Discher8Physical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USAPhysical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USAPhysical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USAPhysical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USAPhysical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USAPhysical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USAPhysical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USAPhysical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USAPhysical Sciences Oncology Center at Penn (PSOC@penn), University of Pennsylvania, Philadelphia, PA, USANuclear rupture has long been associated with deficits or defects in lamins, with recent results also indicating a role for actomyosin stress, but key physical determinants of rupture remain unclear. Here, lamin-B filaments stably interact with the nuclear membrane at sites of low Gaussian curvature yet dilute at high curvature to favor rupture, whereas lamin-A depletion requires high strain-rates. Live-cell imaging of lamin-B1 gene-edited cancer cells is complemented by fixed-cell imaging of rupture in: iPS-derived progeria patients cells, cells within beating chick embryo hearts, and cancer cells with multi-site rupture after migration through small pores. Data fit a model of stiff filaments that detach from a curved surface.Rupture is modestly suppressed by inhibiting myosin-II and by hypotonic stress, which slow the strain-rates. Lamin-A dilution and rupture probability indeed increase above a threshold rate of nuclear pulling. Curvature-sensing mechanisms of proteins at plasma membranes, including Piezo1, might thus apply at nuclear membranes.Summary statement: High nuclear curvature drives lamina dilution and nuclear envelope rupture even when myosin stress is inhibited. Stiff filaments generally dilute from sites of high Gaussian curvature, providing mathematical fits of experiments.https://www.tandfonline.com/doi/10.1080/19491034.2022.2045726curvaturenuclear laminanuclear envelope rupturemyosin stressbiophysical modelmechanobiology |
| spellingShingle | Charlotte R. Pfeifer Michael P. Tobin Sangkyun Cho Manasvita Vashisth Lawrence J. Dooling Lizeth Lopez Vazquez Emma G. Ricci-De Lucca Keiann T. Simon Dennis E. Discher Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate Nucleus curvature nuclear lamina nuclear envelope rupture myosin stress biophysical model mechanobiology |
| title | Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate |
| title_full | Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate |
| title_fullStr | Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate |
| title_full_unstemmed | Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate |
| title_short | Gaussian curvature dilutes the nuclear lamina, favoring nuclear rupture, especially at high strain rate |
| title_sort | gaussian curvature dilutes the nuclear lamina favoring nuclear rupture especially at high strain rate |
| topic | curvature nuclear lamina nuclear envelope rupture myosin stress biophysical model mechanobiology |
| url | https://www.tandfonline.com/doi/10.1080/19491034.2022.2045726 |
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