The densely packed microtubule (MT) array found in neuronal cell projections (neurites) serves two fundamental functions simultaneously: it provides a mechanically stable track for molecular motor-based transport and produces forces that drive neurite growth. The local pattern of MT polarity along the neurite shaft has been found to differ between axons and dendrites. In axons, the neurons' dominating long projections, roughly 90% of the MTs orient with their rapidly growing plus end away from the cell body, whereas in vertebrate dendrites, their orientations are locally mixed. Molecular motors are known to be responsible for cytoskeletal ordering and force generation, but their collective function in the dense MT cytoskeleton of neurites remains elusive. We here hypothesized that both the polarity pattern of MTs along the neurite shaft and the shaft's global extension are simultaneously driven by molecular motor forces and should thus be regulated by the mechanical load acting on the MT array as a whole. To investigate this, we simulated cylindrical bundles of MTs that are cross-linked and powered by molecular motors by iteratively solving a set of force-balance equations. The bundles were subjected to a fixed load arising from actively generated tension in the actomyosin cortex enveloping the MTs. The magnitude of the load and the level of motor-induced connectivity between the MTs have been varied systematically. With an increasing load and decreasing motor-induced connectivity between MTs, the bundles became wider in cross section and extended more slowly, and the local MT orientational order was reduced. These results reveal two, to our knowledge, novel mechanical factors that may underlie the distinctive development of the MT cytoskeleton in axons and dendrites: the cross-linking level of MTs by motors and the load acting on this cytoskeleton during growth.

中文翻译：

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神经突极化和生长的机械调节——一项计算研究

在神经元细胞突起（神经突）中发现的密集微管 (MT) 阵列同时具有两个基本功能：它为基于分子运动的运输提供机械稳定的轨道，并产生驱动神经突生长的力。已发现沿轴突轴的 MT 极性的局部模式在轴突和树突之间有所不同。在轴突中，神经元占主导地位的长投影，大约 90% 的 MT 以其快速增长的正端远离细胞体而定向，而在脊椎动物树突中，它们的定向是局部混合的。已知分子马达负责细胞骨架的排序和力的产生，但它们在神经突的密集 MT 细胞骨架中的集体功能仍然难以捉摸。我们在这里假设沿着轴突轴的 MT 的极性模式和轴的全局延伸同时由分子马达力驱动，因此应该由作用在整个 MT 阵列上的机械负载调节。为了研究这一点，我们通过迭代求解一组力平衡方程来模拟交联并由分子马达驱动的圆柱形 MTs 束。束受到由包裹 MT 的肌动球蛋白皮层中主动产生的张力引起的固定载荷。负载的大小和 MT 之间的电机感应连接水平已系统地变化。随着负载的增加和 MT 之间运动诱发的连接性的降低，束的横截面变得更宽，并且延伸得更慢，并且局部 MT 定向顺序降低。据我们所知，这些结果揭示了两个新的机械因素，它们可能是轴突和树突中 MT 细胞骨架独特发展的基础：马达的 MT 交联水平和生长过程中作用于该细胞骨架的负载。