Mammalian cells frequently migrate through tight spaces during normal embryogenesis, wound healing, diapedesis, or in pathological situations such as metastasis. Nuclear size and shape are important factors in regulating the mechanical properties of cells during their migration through such tight spaces. At the onset of migratory behavior, cells often initiate the expression of vimentin, an intermediate filament protein that polymerizes into networks extending from a juxtanuclear cage to the cell periphery. However, the role of vimentin intermediate filaments (VIFs) in regulating nuclear shape and mechanics remains unknown. Here, we use wild-type and vimentin-null mouse embryonic fibroblasts to show that VIFs regulate nuclear shape and perinuclear stiffness, cell motility in 3D, and the ability of cells to resist large deformations. These changes increase nuclear rupture and activation of DNA damage repair mechanisms, which are rescued by exogenous reexpression of vimentin. Our findings show that VIFs provide mechanical support to protect the nucleus and genome during migration.
Vimentin protects cells against nuclear rupture and DNA damage during migration
A.E. Patteson and A. Vahabikashi contributed equally to this paper.
- Views Icon Views
- Share Icon Share
- Tools Icon Tools
- Search Site
Alison E. Patteson, Amir Vahabikashi, Katarzyna Pogoda, Stephen A. Adam, Kalpana Mandal, Mark Kittisopikul, Suganya Sivagurunathan, Anne Goldman, Robert D. Goldman, Paul A. Janmey; Vimentin protects cells against nuclear rupture and DNA damage during migration. J Cell Biol 2 December 2019; 218 (12): 4079–4092. doi: https://doi.org/10.1083/jcb.201902046
Download citation file: