Cytotoxic T lymphocytes (T) and natural killer cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (i.e., target cells). Once a natural killer or T cell has identified a target cell, they form a tight contact zone, the immunological synapse (IS). One then observes a repolarization of the cell involving the rotation of the microtubule (MT) cytoskeleton and a movement of the MT organizing center (MTOC) to a position that is just underneath the plasma membrane at the center of the IS. Concomitantly, a massive relocation of organelles attached to MTs is observed, including the Golgi apparatus, lytic granules, and mitochondria. Because the mechanism of this relocation is still elusive, we devise a theoretical model for the molecular-motor-driven motion of the MT cytoskeleton confined between plasma membrane and nucleus during T cell polarization. We analyze different scenarios currently discussed in the literature, the cortical sliding and capture-shrinkage mechanisms, and compare quantitative predictions about the spatiotemporal evolution of MTOC position and MT cytoskeleton morphology with experimental observations. The model predicts the experimentally observed biphasic nature of the repositioning due to an interplay between MT cytoskeleton geometry and motor forces and confirms the dominance of the capture-shrinkage over the cortical sliding mechanism when the MTOC and IS are initially diametrically opposed. We also find that the two mechanisms act synergistically, thereby reducing the resources necessary for repositioning. Moreover, it turns out that the localization of dyneins in the peripheral supramolecular activation cluster facilitates their interaction with the MTs. Our model also opens a way to infer details of the dynein distribution from the experimentally observed features of the MT cytoskeleton dynamics. In a subsequent publication, we will address the issue of general initial configurations and situations in which the T cell established two ISs.

中文翻译：

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目标消除过程中 T 细胞复极化的随机模型 (I)

细胞毒性T淋巴细胞（T）和自然杀伤细胞是人体主要的细胞毒性杀伤细胞，用于清除病原体感染或致瘤细胞（即靶细胞）。一旦自然杀伤细胞或 T 细胞识别出目标细胞，它们就会形成一个紧密的接触区，即免疫突触 (IS)。然后观察到细胞的复极化，涉及微管 (MT) 细胞骨架的旋转和 MT 组织中心 (MTOC) 移动到位于 IS 中心的质膜下方的位置。同时，观察到附着在 MTs 上的细胞器大量迁移，包括高尔基体、裂解颗粒和线粒体。因为这种重定位的机制仍然难以捉摸，我们设计了一个理论模型，用于在 T 细胞极化期间限制在质膜和细胞核之间的 MT 细胞骨架的分子马达驱动运动。我们分析了目前在文献中讨论的不同场景，即皮质滑动和捕获收缩机制，并将关于 MTOC 位置和 MT 细胞骨架形态的时空演变的定量预测与实验观察进行比较。该模型预测了由于 MT 细胞骨架几何形状和运动力之间的相互作用而导致的重新定位的实验观察到的双相性质，并证实了当 MTOC 和 IS 最初完全相反时，捕获收缩在皮质滑动机制上的优势。我们还发现这两种机制协同作用，从而减少了重新定位所需的资源。此外，事实证明，动力蛋白在外周超分子激活簇中的定位促进了它们与 MT 的相互作用。我们的模型还开辟了一种从 MT 细胞骨架动力学的实验观察特征推断动力蛋白分布细节的方法。在随后的出版物中，我们将讨论 T 细胞建立两个 IS 的一般初始配置和情况。