The mechanisms by which cells exert forces on their nuclei to migrate through openings smaller than the nuclear diameter remain unclear. We use CRISPR/Cas9 to fluorescently label nesprin‐2 giant, which links the cytoskeleton to the nuclear interior. We demonstrate that nesprin‐2 accumulates at the front of the nucleus during nuclear deformation through narrow constrictions, independently of the nuclear lamina. We find that nesprins are mobile at time scales similar to the accumulation. Using artificial constructs, we show that the actin‐binding domain of nesprin‐2 is necessary and sufficient for this accumulation. Actin filaments are organized in a barrel structure around the nucleus in the direction of movement. Using two‐photon ablation and cytoskeleton‐inhibiting drugs, we demonstrate an actomyosin‐dependent pulling force on the nucleus from the front of the cell. The elastic recoil upon ablation is dampened when nesprins are reduced at the nuclear envelope. We thus show that actin redistributes nesprin‐2 giant toward the front of the nucleus and contributes to pulling the nucleus through narrow constrictions, in concert with myosin.

中文翻译：

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在有限的细胞迁移过程中，Nesprin-2积聚在细胞核的前端。

细胞在细胞核上施加力以通过小于核直径的开口迁移的机制仍然不清楚。我们使用CRISPR / Cas9荧光标记nesprin-2巨人，该巨人将细胞骨架连接到核内部。我们证明，nesprin-2在狭窄的收缩过程中通过狭窄的收缩而聚集在核的前部，与核层无关。我们发现，雀巢蛋白在类似于累积的时间尺度上是可移动的。使用人工构建体，我们表明nesprin-2的肌动蛋白结合域对于这种积累是必要和充分的。肌动蛋白丝沿运动方向以桶形结构围绕核分布。使用双光子消融和抑制细胞骨架的药物，我们证明了从细胞前部对核的放线菌素依赖性拉力。当雀巢蛋白在核包膜处减少时，消融后的弹性反冲力会减弱。因此，我们表明肌动蛋白与肌球蛋白一起将nesprin-2巨噬细胞重新分配到细胞核的前部，并有助于通过狭窄的颈缩拉动细胞核。