Nuclei within cells are constantly subjected to compressive, tensile, and shear forces, which regulate nucleoskeletal and cytoskeletal remodeling, activate signaling pathways, and direct cell-fate decisions. Multiple rheological methods have been adapted for characterizing the response to applied forces of isolated nuclei and nuclei within intact cells. However, in vitro measurements fail to capture the viscoelastic modulation of nuclear stress-strain relationships by the physiological tethering to the surrounding cytoskeleton, extracellular matrix and cells, and tissue-level architectures. Using an equiaxial stretching apparatus, we applied a step stress and measured nucleus deformation dynamics within living Caenorhabditis elegans nematodes. Nuclei deformed nonmonotonically under constant load. Nonmonotonic deformation was conserved across tissues and robust to nucleoskeletal and cytoskeletal perturbations, but it required intact linker of nucleoskeleton and cytoskeleton complex attachments. The transition from creep to strain recovery fits a tensile-compressive linear viscoelastic model that is indicative of nucleoskeletal-cytoskeletal decoupling under high load. Ce-lamin (lmn-1) knockdown softened the nucleus, whereas nematode aging stiffened the nucleus and decreased deformation recovery rate. Recovery lasted minutes rather than seconds due to physiological damping of the released mechanical energy, thus protecting nuclear integrity and preventing chromatin damage.

中文翻译：

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测量活的多细胞生物体内的核力学：物理去耦和衰减的恢复速率是高机械负荷下细胞核的生理保护机制。

细胞内的核不断受到压缩力，拉伸力和剪切力的作用，它们调节核骨架和细胞骨架的重塑，激活信号传导途径，并直接决定细胞命运。已采用多种流变方法来表征对孤立细胞核和完整细胞内细胞核施加力的响应。但是，体外测量无法通过与周围细胞骨架，细胞外基质和细胞以及组织水平结构的生理系链来捕获核应力-应变关系的粘弹性调制。使用等轴拉伸设备，我们施加了阶梯应力，并测量了活的秀丽隐杆线虫线虫内的核变形动力学。核在恒定载荷下非单调变形。非单调变形在组织间保守，对核骨架和细胞骨架扰动具有鲁棒性，但它需要完整的核骨架和细胞骨架复合物附件连接体。从蠕变到应变恢复的过渡拟合了拉伸-压缩线性粘弹性模型，该模型指示了高载荷下核骨架-细胞骨架解耦。Ce-lamin（lmn-1）组合体软化了核，而线虫老化则使核变硬，降低了变形回复率。由于释放的机械能的生理阻尼，恢复持续了几分钟而不是几秒钟，从而保护了核的完整性并防止了染色质的破坏。从蠕变到应变恢复的过渡拟合了拉伸-压缩线性粘弹性模型，该模型指示了高载荷下核骨架-细胞骨架解耦。Ce-lamin（lmn-1）组合体软化了核，而线虫老化则使核变硬，降低了变形回复率。由于释放的机械能的生理阻尼，恢复持续了几分钟而不是几秒钟，从而保护了核的完整性并防止了染色质的破坏。从蠕变到应变恢复的过渡拟合了拉伸-压缩线性粘弹性模型，该模型指示在高负荷下核骨架-细胞骨架解耦。Ce-lamin（lmn-1）组合体软化了核，而线虫老化则使核变硬，降低了变形回复率。由于释放的机械能的生理阻尼，恢复持续了几分钟而不是几秒钟，从而保护了核的完整性并防止了染色质的破坏。