Motile cells encounter microenvironments with locally heterogeneous mechanochemical composition. Individual compositional parameters, such as chemokines and extracellular matrix pore sizes, are well known to provide guidance cues for pathfinding. However, motile cells face diverse cues at the same time, raising the question of how they respond to multiple and potentially competing signals on their paths. Here, we reveal that amoeboid cells require nuclear repositioning, termed nucleokinesis, for adaptive pathfinding in heterogeneous mechanochemical micro-environments. Using mammalian immune cells and the amoeba Dictyostelium discoideum, we discover that frequent, rapid and long-distance nucleokinesis is a basic component of amoeboid pathfinding, enabling cells to reorientate quickly between locally competing cues. Amoeboid nucleokinesis comprises a two-step polarity switch and is driven by myosin-II forces that readjust the nuclear to the cellular path. Impaired nucleokinesis distorts path adaptions and causes cellular arrest in the microenvironment. Our findings establish that nucleokinesis is required for amoeboid cell navigation. Given that many immune cells, amoebae, and some cancer cells utilize an amoeboid migration strategy, these results suggest that nucleokinesis underlies cellular navigation during unicellular biology, immunity, and disease.

中文翻译：

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变形虫迁移过程中通过核运动进行适应性寻路

运动细胞遇到具有局部异质机械化学成分的微环境。众所周知，单个成分参数（例如趋化因子和细胞外基质孔径）可以为寻路提供指导线索。然而，运动细胞同时面临着不同的线索，这就提出了它们如何响应路径上多个潜在竞争信号的问题。在这里，我们揭示了变形虫细胞需要核重新定位，称为核运动，以便在异质机械化学微环境中进行适应性寻路。利用哺乳动物免疫细胞和变形虫盘基网柄菌，我们发现频繁、快速和长距离的核运动是变形虫寻路的基本组成部分，使细胞能够在局部竞争线索之间快速重新定向。变形虫核分裂由两步极性开关组成，由肌球蛋白-II 力驱动，将核重新调整到细胞路径。核运动受损会扭曲路径适应并导致微环境中的细胞停滞。我们的研究结果表明，阿米巴细胞导航需要核运动。鉴于许多免疫细胞、变形虫和一些癌细胞利用变形虫迁移策略，这些结果表明核运动是单细胞生物学、免疫和疾病期间细胞导航的基础。