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.

中文翻译：

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波形蛋白可保护细胞在迁移过程中免受核破裂和 DNA 损伤

在正常胚胎发生、伤口愈合、血细胞渗出或转移等病理情况下，哺乳动物细胞经常在狭窄的空间中迁移。细胞核的大小和形状是调节细胞在如此狭小空间迁移过程中机械性能的重要因素。在迁移行为开始时，细胞通常会启动波形蛋白的表达，波形蛋白是一种中间丝蛋白，聚合成从核旁笼延伸到细胞外围的网络。然而，波形蛋白中间丝（VIF）在调节核形状和力学中的作用仍然未知。在这里，我们使用野生型和波形蛋白缺失的小鼠胚胎成纤维细胞来证明 VIF 调节核形状和核周硬度、3D 细胞运动以及细胞抵抗大变形的能力。这些变化增加了核破裂和 DNA 损伤修复机制的激活，这些机制可以通过波形蛋白的外源重新表达来挽救。我们的研究结果表明，VIF 提供机械支持以在迁移过程中保护细胞核和基因组。