Mechanosensing has been recently explored for T cells and B cells and is believed to be a part of their activation mechanism. Here, we investigated the mechanosensing of the third type of lymphocyte – natural killer (NK) cells, by showing that they modulate their immune activity in response to changes in the stiffness of a stimulating surface. Interestingly, we found that this immune response is bell-shaped and peaks for a stiffness of a few hundreds of kPa. This bell-shaped behavior was observed only for surfaces functionalized with the activating ligand major histocompatibility complex class I polypeptide-related sequence A but not for control surfaces, lacking immunoactive functionalities. We found that stiffness does not affect uniformly all the cells but increases the size of a little group of extra-active cells, which in turn contributes to the overall activation effect of the entire cell population. We further imaged the clustering of costimulatory adapter protein DAP10 on the NK cell membrane and found the same bell-shaped dependence to surface stiffness. Our findings reveal what seems to be ″the tip of the iceberg″ of mechanosensation of NK cells and provide an important insight into the mechanism of their immune signaling.

中文翻译：

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机械调节自然杀伤细胞的细胞毒活性

最近已经研究了针对T细胞和B细胞的机械传感，并认为这是其激活机制的一部分。在这里，我们研究了第三种类型的淋巴细胞-自然杀伤（NK）细胞的机械传感，方法是显示它们响应刺激表面的硬度变化来调节其免疫活性。有趣的是，我们发现这种免疫反应呈钟形，并在几百kPa的硬度下达到峰值。仅在用活化配体主要组织相容性复合物I类多肽相关序列A功能化的表面上观察到这种钟形行为，而在缺乏免疫活性功能的对照表面上未观察到。我们发现刚度并不会均匀地影响所有细胞，但会增加一小部分活跃细胞的大小，进而有助于整个细胞群体的整体活化作用。我们进一步成像了共刺激衔接蛋白DAP10在NK细胞膜上的聚类，发现对表面硬度的钟形依赖性相同。我们的发现揭示了似乎是NK细胞机械传感的“冰山一角”，并为他们的免疫信号传导机制提供了重要的见识。