Department of Theoretical Physics and Center for Biophysics, Universität des Saarlandes, Saarbrücken, Saarland, Germany.
Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, School of Medicine, Universität des Saarlandes, Homburg, Saarland, Germany.
Biophys J. 2020 Dec 1;119(11):2141-2152. doi: 10.1016/j.bpj.2020.10.020.
CD8 cytotoxic T lymphocytes (CTL) and natural killer cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (also known as target cells). To find their targets, they have to navigate and migrate through 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.
CD8 细胞毒性 T 淋巴细胞（CTL）和自然杀伤细胞是人体消除病原体感染或肿瘤细胞（也称为靶细胞）的主要细胞毒性杀伤细胞。为了找到它们的靶标，它们必须在复杂的生物微环境中导航和迁移，其中一个关键组成部分是细胞外基质（ECM）。杀伤细胞导航的机制尚不清楚。为了模拟 ECM，我们使用由不同浓度胶原形成的基质，并分析原代人 CTL 的迁移轨迹。观察到不同的迁移模式，并可分为三种运动类型：缓慢、快速和混合。双态持续随机行走模型很好地描述了动力学，该模型允许细胞在低持久性的缓慢运动和高持久性的快速运动之间切换。我们假设缓慢的运动模式描述了 CTL 通过变形和撕裂胶原纤维在胶原基质中创建通道的过程，而快速的运动模式描述了 CTL 在这些通道内的运动。通过可视化在完全相同的轨迹上相互跟随的迁移 T 细胞，并显示细胞在周围胶原基质中的类似通道的腔室内快速移动，提供了支持这种情况的实验证据。因此，CTL 在 ECM 中的随机搜索过程的效率应该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。
