CD8+ cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (= target cells). To find their targets they have to navigate and migrate through a complex biological microenvironments, a key component of which is the extracellular matrix (ECM). The mechanisms underlying killer cell's navigation are not well understood. To mimic an ECM we use a matrix formed by different collagen concentrations, and analyze migration trajectories of primary human CTLs. Different migration patterns are observed and can be grouped into three motility types: slow, fast and mixed. The dynamics are well described by a two-state persistent random walk model which allows cells to switch between slow motion with low persistence, and fast motion with high persistence. We hypothesize that the slow motility mode describes CTLs creating channels through the collagen matrix by deforming and tearing apart collagen fibers, and that the fast motility mode describes CTLs moving within these channels. Experimental evidence supporting this scenario is presented by visualizing migrating T cells following each other on exactly the same track and showing cells moving quickly in channel-like cavities within the surrounding collagen matrix. Consequently, the efficiency of the stochastic search process of CTLs in the ECM should strongly be influenced by a dynamically changing channel network produced by the killer cells themselves.

中文翻译：

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细胞毒性T淋巴细胞在3D胶原蛋白基质中的迁移

CD8 +细胞毒性T淋巴细胞（CTL）和自然杀伤（NK）细胞是人体消除病原体感染或致瘤细胞（=目标细胞）的主要细胞毒杀伤细胞。为了找到他们的靶标，他们必须在复杂的生物微环境中导航和迁移，其中的关键组成部分是细胞外基质（ECM）。杀手细胞的导航机制尚不清楚。为了模拟ECM，我们使用由不同胶原蛋白浓度形成的基质，并分析主要人类CTL的迁移轨迹。观察到了不同的迁移模式，可以将其分为三种运动类型：慢，快和混合。动态状态可以通过两种状态的持久随机游动模型很好地描述，该模型允许细胞以低持久性在慢动作之间进行切换，高持久性的快动作。我们假设慢运动模式描述了CTL通过变形和撕裂胶原纤维而通过胶原基质创建通道，而快速运动模式描述了CTL在这些通道内移动。通过可视化在完全相同的轨道上彼此跟随的迁移T细胞并显示细胞在周围胶原蛋白基质内的通道状腔中快速移动来提供支持这种情况的实验证据。因此，ECM中CTL随机搜索过程的效率应受到杀伤细胞自身产生的动态变化的通道网络的强烈影响。快速运动模式描述了在这些通道内移动的CTL。通过可视化在完全相同的轨道上彼此跟随的迁移T细胞并显示细胞在周围胶原蛋白基质内的通道状腔中快速移动来提供支持这种情况的实验证据。因此，ECM中CTL随机搜索过程的效率应受到杀伤细胞自身产生的动态变化的通道网络的强烈影响。快速运动模式描述了在这些通道内移动的CTL。通过可视化在完全相同的轨道上彼此跟随的迁移T细胞并显示细胞在周围胶原蛋白基质内的通道状腔中快速移动来提供支持这种情况的实验证据。因此，ECM中CTL随机搜索过程的效率应受到杀伤细胞自身产生的动态变化的通道网络的强烈影响。