Demonstration of mechanical connections between integrins cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure
Demonstration of mechanical connections between integrins cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure
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DOI：
10.1073/pnas.94.3.849
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发表时间：
1997-02-04
影响因子：
11.1
通讯作者：
Ingber, DE
中科院分区：
文献类型：
--
作者：
Maniotis, AJ;Chen, CS;Ingber, DE
我们在此报道，活细胞和细胞核是紧密相连的，以至于对细胞表面受体的机械牵拉能够立即改变细胞质和细胞核中分子组装体的组织形式。当通过显微操作结合的微珠或微量移液器牵拉整合素时，细胞骨架丝会重新定向，细胞核会变形，核仁会沿着所施加的张力场方向重新分布。这些效应是整合素所特有的，与皮质膜变形无关，并且是由细胞骨架和细胞核之间的直接连接所介导的。肌动蛋白微丝在低应变下介导力向细胞核的传递；然而，肌动蛋白凝胶在更大变形时会撕裂。相比之下，中间丝在这两种情况下都能有效地介导力向细胞核的传递。这些丝系统还作为分子牵索来使细胞核在机械上变硬并将其固定在适当位置，而微管则起到撑开中间丝晶格并使细胞核在抵抗侧向压缩时保持稳定的作用。因此，整合素、细胞骨架丝和核支架之间的分子连接可能为机械信号在细胞内的传递提供了一条特定的路径，以及一种在细胞外基质黏附性或力学性质发生变化时使细胞和细胞核结构产生整体性改变的机制。
We report here that living cells and nuclei are hard-wired such that a mechanical tug on cell surface receptors can immediately change the organization of molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by micromanipulating bound microbeads or micropipettes, cytoskeletal filaments reoriented, nuclei distorted, and nucleoli redistributed along the axis of the applied tension field. These effects were specific for integrins, independent of cortical membrane distortion, and were mediated by direct linkages between the cytoskeleton and nucleus. Actin microfilaments mediated force transfer to the nucleus at low strain; however, tearing of the actin gel resulted with greater distortion. In contrast, intermediate filaments effectively mediated force transfer to the nucleus under both conditions. These filament systems also acted as molecular guy wires to mechanically stiffen the nucleus and anchor it in place, whereas microtubules acted to hold open the intermediate filament lattice and to stabilize the nucleus against lateral compression. Molecular connections between integrins, cytoskeletal filaments, and nuclear scaffolds may therefore provide a discrete path for mechanical signal transfer through cells as well as a mechanism for producing integrated changes in cell and nuclear structure in response to changes in extracellular matrix adhesivity or mechanics.