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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mechanical impulses can control metaphase progression in a mammalian cell
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Mechanical impulses can control metaphase progression in a mammalian cell

机译:机械冲动可以控制哺乳动物细胞的中期进程

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摘要

Chromosome segregation machinery is controlled by mechano-chemical regulation. Tension in a mitotic spindle, which is balanced by molecular motors and polymerization-depolymerization dynamics of microtubules, is thought to be essential for determining the timing of chromosome segregation after the establishment of the kinetochore-microtubule attachments. It is not known, however, whether and how applied mechanical forces modulate the tension balance and chemically affect the molecular processes involved in chromosome segregation. Here we found that a mechanical impulse externally applied to mitotic HeLa cells alters the balance of forces within the mitotic spindle. We identified two distinct mitotic responses to the applied mechanical force that either facilitate or delay anaphase onset, depending on the direction of force and the extent of cell compression. An external mechanical impulse that physically increases tension within the mitotic spindle accelerates anaphase onset, and this is attributed to the facilitation of physical cleavage of sister chromatid cohesion. On the other hand, a decrease in tension activates the spindle assembly checkpoint, which impedes the degradation of mitotic proteins and delays the timing of chromosome segregation. Thus, the external mechanical force acts as a crucial regulator for metaphase progression, modulating the internal force balance and thereby triggering specific mechanochemical cellular reactions.
机译:染色体分离机制由机械化学调节控制。有丝分裂纺锤体中的张力受分子马达和微管的聚合-解聚动力学平衡,被认为对于确定动粒-微管附件建立后染色体分离的时机至关重要。然而,尚不知道施加的机械力是否以及如何调节张力平衡并化学影响染色体分离所涉及的分子过程。在这里,我们发现从外部施加到有丝分裂HeLa细胞的机械冲动改变了有丝分裂纺锤体内力的平衡。我们确定了对施加的机械力的两种不同的有丝分裂反应,这些反应可以促进或延迟后期发作,具体取决于作用力的方向和细胞受压的程度。物理上增加有丝分裂纺锤体内部张力的外部机械冲动会加速后期发生,这归因于姐妹染色单体凝聚力的物理裂解。另一方面,张力的降低会激活纺锤体装配检查点,这会阻止有丝分裂蛋白的降解并延迟染色体分离的时间。因此,外部机械力充当中期进程的关键调节器,调节内部力平衡,从而触发特定的机械化学细胞反应。

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  • 作者单位

    Department of Physics , Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan;

    Department of Chemistry and Biochemistry, Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan;

    Graduate School of Information Science and Technology, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan;

    Graduate School of Information Science and Technology, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan;

    Graduate School of Information Science and Technology, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656, Japan;

    Department of Physics , Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan,Waseda Bioscience Research Institute in Singapore, 11 Biopolis Way, #05-01/02 Helios, Singapore 138667;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    chromosome segregation; mechanobiology; mitotic force; mitotic spindle; spindle assembly checkpoint;

    机译:染色体分离机械生物学有丝分裂力有丝分裂纺锤体;主轴组件检查点;

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