检测迁移细胞之间的长程相互作用
Detecting long-range interactions between migrating cells
摘要：
趋化性使细胞能够系统地接近发射可扩散引导物质的远处目标。然而，目视观察细胞和靶标之间的相遇并不一定表明存在趋化性接近机制，因为即使是盲目迁移的细胞也可能偶然遇到靶标。为了区分趋化方法和盲目迁移，我们提出了一种客观的方法，是基于分析的时间推移记录的细胞迁移轨迹。首先，我们用模拟数据验证了我们的方法，证明它可靠地检测到远程细胞间相互作用的存在或不存在。在第二步中，我们将该方法应用于来自三维胶原凝胶的数据，其中散布着来自两个不同人类供体的高度迁移的自然杀伤（NK）细胞。我们发现其中一个供体的NK细胞之间有吸引力的相互作用，指向这些免疫细胞的合作行为。当将几乎静止的K562肿瘤细胞加入到系统中时，我们发现K562和其中一个供体的NK细胞之间存在排斥相互作用。相比之下，我们发现NK细胞和K562肿瘤细胞的IL-15分泌变体之间有吸引力的相互作用。因此，我们推测NK细胞只是偶然发现野生型肿瘤细胞，但在近距离接触后会迅速离开目标。我们提供了一个免费的p-value方法的Python实现，它可以作为一个通用工具，用于检测自驱动代理的集体系统中的远程交互。
英文摘要：
Chemotaxis enables cells to systematically approach distant targets that emit a diffusible guiding substance. However, the visual observation of an encounter between a cell and a target does not necessarily indicate the presence of a chemotactic approach mechanism, as even a blindly migrating cell can come across a target by chance. To distinguish between the chemotactic approach and blind migration, we present an objective method that is based on the analysis of time-lapse recorded cell migration trajectories. First, we validate our method with simulated data, demonstrating that it reliably detects the presence or absence of remote cell-cell interactions. In a second step, we apply the method to data from three-dimensional collagen gels, interspersed with highly migratory natural killer (NK) cells that were derived from two different human donors. We find for one of the donors an attractive interaction between the NK cells, pointing to a cooperative behavior of these immune cells. When adding nearly stationary K562 tumor cells to the system, we find a repulsive interaction between K562 and NK cells for one of the donors. By contrast, we find attractive interactions between NK cells and an IL-15-secreting variant of K562 tumor cells. We therefore speculate that NK cells find wild-type tumor cells only by chance, but are programmed to leave a target quickly after a close encounter. We provide a freely available Python implementation of our p-value method that can serve as a general tool for detecting long-range interactions in collective systems of self-driven agents.
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