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- W3092332425 abstract "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." @default.
- W3092332425 created "2020-10-15" @default.
- W3092332425 creator A5049714719 @default.
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- W3092332425 date "2020-10-09" @default.
- W3092332425 modified "2023-10-15" @default.
- W3092332425 title "Nuclear plasticity increases susceptibility to damage during confined migration" @default.
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- W3092332425 doi "https://doi.org/10.1371/journal.pcbi.1008300" @default.
- W3092332425 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7577492" @default.
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- W3092332425 hasPublicationYear "2020" @default.
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