Mechanical Regulation of the Cytotoxic Activity of Natural Killer Cells

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.