Prestress mediates force propagation into the nucleus

Prestress mediates force propagation into the nucleus
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DOI:
10.1016/j.bbrc.2005.02.026
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发表时间:
2005-04-08
影响因子:
3.1
通讯作者:
Wang, N
Wang, N
中科院分区:
生物学4区
文献类型:
--
作者:
Hu, SH;Chen, JX;Wang, N

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一些报告表明,细胞核比细胞质硬10倍。因此,尚不清楚核内结构是否可以通过生理量级的载荷直接变形。如果生理负荷不能直接使核内结构变形,则核内的信号传导将仅通过扩散或移位机制发生。使用同步检测的方法,我们量化的位移核仁结构在培养的气道平滑肌细胞在响应本地化的生理负荷(类似于0.4 μ m的表面变形)通过整合素受体。核仁有明显的移位。核仁结构也表现出显着的变形,与占主导地位的应变是体应变。增加细胞骨架中预先存在的张应力(预应力)显着增加了对核仁的应力传播效率(定义为每表面变形的核仁位移),而降低预应力显着降低了对核仁的应力传播效率。废除应力纤维/肌动蛋白束通过将细胞铺在聚-L-赖氨酸包被的培养皿上显著抑制应力传播到核仁。这些结果表明,在细胞骨架中的预应力是至关重要的介导应力传播到核仁,直接机械调节核活动和功能的影响。(c)2005年爱思唯尔公司All rights reserved.
Several reports show that the nucleus is 10 times stiffer than the cytoplasm. Hence, it is not clear if intra-nuclear structures can be directly deformed by a load of physiologic magnitudes. If a physiologic load could not directly deform intra-nuclear structures, then signaling inside the nucleus would occur only via the mechanisms of diffusion or translocation. Using a synchronous detection approach, we quantified displacements of nucleolar structures in cultured airway smooth muscle cells in response to a localized physiologic load (similar to 0.4 mu m surface deformation) via integrin receptors. The nucleolus exhibited significant displacements. Nucleolar structures also exhibited significant deformation, with the dominant strain being the bulk strain. Increasing the pre-existing tensile stress (prestress) in the cytoskeleton significantly increased the stress propagation efficiency to the nucleolus (defined as nucleolus displacement per surface deformation) whereas decreasing the prestress significantly lowered the stress propagation efficiency to the nucleolus. Abolishing the stress fibers/actin bundles by plating the cells on poly-L-lysine-coated dishes dramatically inhibited stress propagation to the nucleolus. These results demonstrate that the prestress in the cytoskeleton is crucial in mediating stress propagation to the nucleolus, with implications for direct mechanical regulation of nuclear activities and functions. (c) 2005 Elsevier Inc. All rights reserved.