Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration
Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration
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DOI：
10.1529/biophysj.106.102426
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Wirtz, Denis
中科院分区：
文献类型：
--
作者：
Lee, Jerry S. H.;Hale, Christopher M.;Wirtz, Denis
核素A/C是核层的主要成分，是一种薄层。位于核膜下的可悲的蛋白质层。在这里，我们显示了小鼠胚胎中层蛋白A/C缺陷。成纤维细胞(Lmna(-/)-MEFS)减弱了这些细胞在伤口边缘极化的能力，并显著降低了细胞向伤口的迁移速度。此外，Lamin A/C de.温度引起微管组织中心(MTOC)与核膜的明显分离。用弹道细胞内纳米流变学的研究表明，Lamin A/C de.细胞毒性还显著影响细胞质的微观机械性质。在Lmna(-/-)MEF中，细胞质的弹性(伸缩性)和粘性(材料的流动倾向)都显著降低。任何一种肌动蛋白的分解。Lmna(+/+)MEF中的细丝或微管网络导致细胞质弹性和粘度下降，降至Lmna(-/)-MEF的水平。综上所述，这些结果表明，细胞骨架和基于细胞骨架的过程的力学性质，包括细胞运动、MTOC和核的耦合动力学以及细胞极化，都严重依赖于核层的完整性，这表明细胞核和细胞骨架之间存在功能上的机械连接。这些结果还表明，细胞迁移过程中的细胞极化需要MTOC与细胞核之间的紧密机械偶联，这种偶联是由Lamin A/C介导的。
Lamin A/C is a major constituent of the nuclear lamina, a thin. lamentous protein layer that lies beneath the nuclear envelope. Here we show that lamin A/C deficiency in mouse embryonic. broblasts (Lmna(-/)-MEFs) diminishes the ability of these cells to polarize at the edge of a wound and significantly reduces cell migration speed into the wound. Moreover, lamin A/C de. ciency induces significant separation of the microtubule organizing center (MTOC) from the nuclear envelope. Investigations using ballistic intracellular nanorheology reveal that lamin A/C de. ciency also dramatically affects the micromechanical properties of the cytoplasm. Both the elasticity (stretchiness) and the viscosity (propensity of a material to flow) of the cytoplasm in Lmna(-/-) MEFs are significantly reduced. Disassembly of either the actin. lament or microtubule networks in Lmna(+/+) MEFs results in decrease of cytoplasmic elasticity and viscosity down to levels found in Lmna(-/)-MEFs. Together these results show that both the mechanical properties of the cytoskeleton and cytoskeleton-based processes, including cell motility, coupled MTOC and nucleus dynamics, and cell polarization, depend critically on the integrity of the nuclear lamina, which suggest the existence of a functional mechanical connection between the nucleus and the cytoskeleton. These results also suggest that cell polarization during cell migration requires tight mechanical coupling between MTOC and nucleus, which is mediated by lamin A/C.