Athale Chaitanya A, Dinarina Ana, Nedelec Francois, Karsenti Eric
Division of Biology, IISER Pune, Sai Trinity, Sutarwadi Road, Pashan, Pune 411021, India. Cell Biology and Biophysics Division, EMBL, Meyerhofstrasse 1, D-69117, Heidelberg, Germany.
Phys Biol. 2014 Feb;11(1):016008. doi: 10.1088/1478-3975/11/1/016008. Epub 2014 Jan 29.
Microtubules (MTs) nucleated by centrosomes form star-shaped structures referred to as asters. Aster motility and dynamics is vital for genome stability, cell division, polarization and differentiation. Asters move either toward the cell center or away from it. Here, we focus on the centering mechanism in a membrane independent system of Xenopus cytoplasmic egg extracts. Using live microscopy and single particle tracking, we find that asters move toward chromatinized DNA structures. The velocity and directionality profiles suggest a random-walk with drift directed toward DNA. We have developed a theoretical model that can explain this movement as a result of a gradient of MT length dynamics and MT gliding on immobilized dynein motors. In simulations, the antagonistic action of the motor species on the radial array of MTs leads to a tug-of-war purely due to geometric considerations and aster motility resembles a directed random-walk. Additionally, our model predicts that aster velocities do not change greatly with varying initial distance from DNA. The movement of asymmetric asters becomes increasingly super-diffusive with increasing motor density, but for symmetric asters it becomes less super-diffusive. The transition of symmetric asters from superdiffusive to diffusive mobility is the result of number fluctuations in bound motors in the tug-of-war. Overall, our model is in good agreement with experimental data in Xenopus cytoplasmic extracts and predicts novel features of the collective effects of motor-MT interactions.
由中心体成核的微管形成称为星状体的星形结构。星状体的运动性和动态变化对于基因组稳定性、细胞分裂、极化和分化至关重要。星状体要么向细胞中心移动,要么远离细胞中心。在这里,我们聚焦于非洲爪蟾卵细胞质提取物的膜独立系统中的居中机制。通过实时显微镜观察和单粒子追踪,我们发现星状体向染色质化的DNA结构移动。速度和方向性分布表明这是一种朝着DNA方向漂移的随机游走。我们开发了一个理论模型,该模型可以将这种运动解释为微管长度动态变化梯度以及微管在固定的动力蛋白马达上滑动的结果。在模拟中,马达种类对微管径向阵列的拮抗作用纯粹由于几何因素导致了一场拔河比赛,并且星状体的运动类似于有向随机游走。此外,我们的模型预测星状体速度不会因与DNA的初始距离变化而大幅改变。不对称星状体的运动随着马达密度增加而变得越来越超扩散,但对称星状体则变得超扩散程度降低。对称星状体从超扩散到扩散迁移率转变是拔河比赛中结合马达数量波动的结果。总体而言,我们的模型与非洲爪蟾卵细胞质提取物中的实验数据高度吻合,并预测了马达 - 微管相互作用集体效应的新特征。