建模和机械扰动揭示了空间调节的锚定如何在哺乳动物纺锤体中产生空间上不同的力学
Modeling and mechanical perturbations reveal how spatially regulated anchorage gives rise to spatially distinct mechanics across the mammalian spindle
摘要：
在细胞分裂期间，纺锤体产生力来移动染色体。在哺乳动物中，微管束称为kinetochore-fibers（k-纤维）附着并分离染色体。要做到这一点，k纤维必须牢固地锚定到动态主轴上。我们之前开发了微针操作以机械挑战k纤维锚定，并观察到空间上不同的反应特征，揭示了异质锚定的存在（Suresh et al. 2020）。锚定是如何在空间上精确调节的，以及什么样的力是必要的和足够的，以概括k-纤维对力的反应仍然不清楚。在这里，我们开发了一个粗粒度的k-纤维模型，并结合操纵实验来推断潜在的锚固使用形状分析。通过系统地测试不同的锚定方案，我们发现，仅在K-纤维末端的力是足够的重演未操纵的K-纤维的形状，但不操纵的横向锚定超过3 $μ$ m的长度尺度附近的染色体也是必不可少的。这种锚定有力地保持了染色体附近的k-纤维取向，同时允许围绕极点枢转。锚定在一个较短的长度尺度不能有力地限制旋转附近的染色体，而锚定在整个主轴阻碍在极点枢转。总之，这项工作揭示了空间调节锚定如何在哺乳动物纺锤体中产生空间上不同的力学，我们认为这是功能的关键。
英文摘要：
During cell division, the spindle generates force to move chromosomes. In mammals, microtubule bundles called kinetochore-fibers (k-fibers) attach to and segregate chromosomes. To do so, k-fibers must be robustly anchored to the dynamic spindle. We previously developed microneedle manipulation to mechanically challenge k-fiber anchorage, and observed spatially distinct response features revealing the presence of heterogeneous anchorage (Suresh et al. 2020). How anchorage is precisely spatially regulated, and what forces are necessary and sufficient to recapitulate the k-fiber's response to force remain unclear. Here, we develop a coarse-grained k-fiber model and combine with manipulation experiments to infer underlying anchorage using shape analysis. By systematically testing different anchorage schemes, we find that forces solely at k-fiber ends are sufficient to recapitulate unmanipulated k-fiber shapes, but not manipulated ones for which lateral anchorage over a 3 $μ$m length scale near chromosomes is also essential. Such anchorage robustly preserves k-fiber orientation near chromosomes while allowing pivoting around poles. Anchorage over a shorter length scale cannot robustly restrict pivoting near chromosomes, while anchorage throughout the spindle obstructs pivoting at poles. Together, this work reveals how spatially regulated anchorage gives rise to spatially distinct mechanics in the mammalian spindle, which we propose are key for function.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
