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Cell migration requires cells to navigate crowded three-dimensional environments, forcing them to squeeze through narrow spaces. This presents a mechanical challenge in particular for the nucleus, because it is large and stiff. Cells must correctly position and protect the nucleus while coordinating actomyosin contractility to move through confined spaces.

细胞迁移需要细胞在拥挤的三维环境中导航，迫使它们在狭窄的空间中挤压。这对原子核来说尤其是一个机械挑战，因为它又大又硬。细胞必须正确定位和保护细胞核，同时协调肌动球蛋白的收缩力以通过受限空间。

Despite the prevalence of compression as a mechanical input in cellular environments, our understanding of how cells sense and respond to such forces remains limited. Ju et al. now show that microtubules act as a mechanostat, by adapting their biomechanical properties to resist compressive forces and promote contractility.By tracking endogenously tagged microtubules in highly migratory melanoma cells, they discovered that microtubules initially organize into a cage-like structure encasing the nucleus as the leading edge of the cell moves through a narrow space.

尽管在细胞环境中压缩作为机械输入的普遍存在，但我们对细胞如何感知和响应这些力的理解仍然有限。Ju等人现在表明，微管通过调整其生物力学特性来抵抗压力并促进收缩力，从而起到机械抑制器的作用。通过追踪高度迁移的黑色素瘤细胞中内源性标记的微管，他们发现微管最初组织成笼状结构，当细胞的前缘穿过狭窄的空间时，将细胞核包裹起来。

This configuration forces microtubules into a highly curved conformation, making them prone to damage and prompting the recruitment of cytoplasmic linker-associated proteins (CLASPs). CLASPs are known rescue factors that support microtubule growth and repair in part by enhancing acetylation of lysine 40 (Lys40) of α-tubulin, a modification that increases microtubule stability and flexibility under mechanical stress.

这种构型迫使微管形成高度弯曲的构象，使其易于受损并促进细胞质接头相关蛋白（CLASP）的募集。CLASP是已知的拯救因子，部分通过增强α-微管蛋白赖氨酸40（Lys40）的乙酰化来支持微管的生长和修复，这种修饰可以增加微管在机械应力下的稳定性和柔韧性。

Loss of CLASPs slowed migration through microfabricated confinement channels and caused the rupture of migrating cells, highlighting the necessity of microtubule repair for successful migration through tight spaces..

扣环的丢失减缓了通过微制造的限制通道的迁移，并导致迁移细胞的破裂，突显了微管修复对于通过狭窄空间成功迁移的必要性。。

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ReferencesOriginal articleJu, R. J. et al. Compression-dependent microtubule reinforcement enables cells to navigate confined environments. Nat. Cell Biol. https://doi.org/10.1038/s41556-024-01476-x (2024)Article

参考文献Original articleJu，R。J。等人。依赖压缩的微管增强使细胞能够在有限的环境中导航。自然细胞生物学。https://doi.org/10.1038/s41556-024-01476-x（2024）条

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Lisa Heinke.Rights and permissionsReprints and permissionsAbout this articleCite this articleHeinke, L. CLASPing and squeezing during cell migration.

丽莎·海因克。权利和许可打印和许可本文引用本文Heinke，L。细胞迁移过程中的扣紧和挤压。

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