细胞毒性T淋巴细胞在三维胶原基质中的迁移
Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices
摘要：
细胞毒性T淋巴细胞（CTL）需要在复杂的生物微环境中迁移以寻找其靶细胞，细胞外基质（ECM）是其重要组成部分。CTL的导航机制至今还没有很好的理解。在这里，我们使用胶原蛋白测定作为ECM的模型，并分析不同浓度的胶原蛋白基质中的原代人CTL的迁移轨迹。我们观察到单个T细胞的不同迁移模式。三种不同的运动类型可以区分：慢，快和混合运动。慢CTL在胶原基质内保持几乎静止，并显示出轻微的抗持续运动性，而快CTL快速且持续地移动（即，具有不太大的转向角）。混合型的动力学由慢运动和快运动的周期组成;两种状态都是持续的，但它们有不同的持续性。动力学可以很好地描述了一个两状态持续随机游走模型。通过分析实验数据提取模型参数。模型预测的均方位移与实验测量的均方位移吻合很好，无需任何拟合参数。观察到的两个状态的运动的潜在原因进行了讨论。T细胞在迁移过程中挖掘胶原蛋白并形成通道，这有助于胶原蛋白网络中其他CTL的移动。
英文摘要：
To fulfill their killing functions, cytotoxic T lymphocytes (CTLs) need to migrate to search for their target cells in complex biological microenvironments, a key component of which is extracellular matrix (ECM). The mechanisms underlying CTL's navigation are not well understood so far. Here we use a collagen assay as a model for the ECM and analyze the migration trajectories of primary human CTLs in collagen matrices with different concentrations. We observe different migration patterns for individual T cells. Three different motility types can be distinguished: slow, fast and mixed motilities. Slow CTLs remain nearly stationary within the collagen matrix and show slightly anti-persistent motility, while the fast ones move quickly and persistent (i.e. with not too large turning angles). The dynamics of the mixed type consists of periods of slow and fast motions; both states are persistent, but they have different persistencies. The dynamics can be well described by a two-state persistent random walk model. We extract the parameters of the model by analyzing experimental data. The mean square displacements predicted by the model and those measured experimentally are in very good agreement, without any fitting parameter. Potential reasons for the observed two-state motility are discussed. T cells dig the collagen during their migration and form channels, which facilitate the movement of other CTLs in the collagen network.
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