关键词: clustering dynein forces mechanics metaphase microtubules mitosis orientation spindle

来  源:   DOI:10.1016/j.devcel.2024.05.022

Abstract:
The forces that orient the spindle in human cells remain poorly understood due to a lack of direct mechanical measurements in mammalian systems. We use magnetic tweezers to measure the force on human mitotic spindles. Combining the spindle\'s measured resistance to rotation, the speed at which it rotates after laser ablating astral microtubules, and estimates of the number of ablated microtubules reveals that each microtubule contacting the cell cortex is subject to ∼5 pN of pulling force, suggesting that each is pulled on by an individual dynein motor. We find that the concentration of dynein at the cell cortex and extent of dynein clustering are key determinants of the spindle\'s resistance to rotation, with little contribution from cytoplasmic viscosity, which we explain using a biophysically based mathematical model. This work reveals how pulling forces on astral microtubules determine the mechanics of spindle orientation and demonstrates the central role of cortical dynein clustering.
摘要:
由于哺乳动物系统中缺乏直接的机械测量,因此对人类细胞中纺锤体的定向力知之甚少。我们使用磁性镊子来测量人体有丝分裂纺锤体上的力。结合主轴测得的旋转阻力,激光烧蚀星体微管后旋转的速度,并且对消融微管数量的估计表明,接触细胞皮质的每个微管都受到~5pN的拉力,这表明每个都是由单独的动力装置驱动的。我们发现细胞皮层中动力蛋白的浓度和动力蛋白聚集的程度是纺锤体旋转阻力的关键决定因素,细胞质粘度的贡献很小,我们使用基于生物物理的数学模型来解释。这项工作揭示了星体微管上的拉力如何确定纺锤体方向的力学,并证明了皮质动力蛋白聚类的核心作用。
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