论文标题

3D胶原蛋白矩阵中细胞毒性T淋巴细胞的迁移

Migration of Cytotoxic T Lymphocytes in 3D Collagen Matrices

论文作者

Sadjadi, Z., Zhao, R., Hoth, M., Qu, B., Rieger, H.

论文摘要

为了履行其杀伤功能,细胞毒性T淋巴细胞(CTL)需要迁移以在复杂的生物学微环境中搜索其靶细胞,其中关键成分是细胞外基质(ECM)。到目前为止,CTL导航的基础机制尚未得到很好的了解。在这里,我们使用胶原蛋白测定法作为ECM的模型,并分析具有不同浓度的胶原蛋白矩阵中原代人CTL的迁移轨迹。我们观察到单个T细胞的不同迁移模式。可以区分三种不同的运动类型:缓慢,快速和混合的运动。慢速CTL几乎保持固定在胶原蛋白基质中,并显示出略微抗稳定的运动性,而快速的运动能力迅速移动(即,转弯角度不太大)。混合类型的动力学由缓慢和快速运动的时期组成;两个州都是持久的,但它们具有不同的持久性。可以通过两态持续的随机步行模型来很好地描述动力学。我们通过分析实验数据来提取模型的参数。模型和实验测量的均方位移在没有任何拟合参数的情况下是非常一致的。讨论了观察到的两态运动的潜在原因。 T细胞在其迁移和形成通道的过程中挖掘胶原蛋白,这有助于胶原蛋白网络中其他CTL的运动。

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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