Nuclear plasticity increases susceptibility to damage during confined migration.
Large nuclear deformations during migration through confined spaces have been associated with nuclear membrane rupture and DNA damage. However, the stresses associated with nuclear damage remain unclear. Here, using a quasi-static plane strain finite element model, we map evolution of nuclear shape...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-10-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1008300 |
| _version_ | 1818926847214223360 |
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| author | Abhishek Mukherjee Amlan Barai Ramesh K Singh Wenyi Yan Shamik Sen |
| author_facet | Abhishek Mukherjee Amlan Barai Ramesh K Singh Wenyi Yan Shamik Sen |
| author_sort | Abhishek Mukherjee |
| collection | DOAJ |
| description | Large nuclear deformations during migration through confined spaces have been associated with nuclear membrane rupture and DNA damage. However, the stresses associated with nuclear damage remain unclear. Here, using a quasi-static plane strain finite element model, we map evolution of nuclear shape and stresses during confined migration of a cell through a deformable matrix. Plastic deformation of the nucleus observed for a cell with stiff nucleus transiting through a stiffer matrix lowered nuclear stresses, but also led to kinking of the nuclear membrane. In line with model predictions, transwell migration experiments with fibrosarcoma cells showed that while nuclear softening increased invasiveness, nuclear stiffening led to plastic deformation and higher levels of DNA damage. In addition to highlighting the advantage of nuclear softening during confined migration, our results suggest that plastic deformations of the nucleus during transit through stiff tissues may lead to bending-induced nuclear membrane disruption and subsequent DNA damage. |
| first_indexed | 2024-12-20T03:03:37Z |
| format | Article |
| id | doaj.art-1cd5204ab28346f591448bb63094f2f8 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-20T03:03:37Z |
| publishDate | 2020-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-1cd5204ab28346f591448bb63094f2f82022-12-21T19:55:39ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582020-10-011610e100830010.1371/journal.pcbi.1008300Nuclear plasticity increases susceptibility to damage during confined migration.Abhishek MukherjeeAmlan BaraiRamesh K SinghWenyi YanShamik SenLarge nuclear deformations during migration through confined spaces have been associated with nuclear membrane rupture and DNA damage. However, the stresses associated with nuclear damage remain unclear. Here, using a quasi-static plane strain finite element model, we map evolution of nuclear shape and stresses during confined migration of a cell through a deformable matrix. Plastic deformation of the nucleus observed for a cell with stiff nucleus transiting through a stiffer matrix lowered nuclear stresses, but also led to kinking of the nuclear membrane. In line with model predictions, transwell migration experiments with fibrosarcoma cells showed that while nuclear softening increased invasiveness, nuclear stiffening led to plastic deformation and higher levels of DNA damage. In addition to highlighting the advantage of nuclear softening during confined migration, our results suggest that plastic deformations of the nucleus during transit through stiff tissues may lead to bending-induced nuclear membrane disruption and subsequent DNA damage.https://doi.org/10.1371/journal.pcbi.1008300 |
| spellingShingle | Abhishek Mukherjee Amlan Barai Ramesh K Singh Wenyi Yan Shamik Sen Nuclear plasticity increases susceptibility to damage during confined migration. PLoS Computational Biology |
| title | Nuclear plasticity increases susceptibility to damage during confined migration. |
| title_full | Nuclear plasticity increases susceptibility to damage during confined migration. |
| title_fullStr | Nuclear plasticity increases susceptibility to damage during confined migration. |
| title_full_unstemmed | Nuclear plasticity increases susceptibility to damage during confined migration. |
| title_short | Nuclear plasticity increases susceptibility to damage during confined migration. |
| title_sort | nuclear plasticity increases susceptibility to damage during confined migration |
| url | https://doi.org/10.1371/journal.pcbi.1008300 |
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