Nanowire Based Guidance of the Morphology and Cytotoxic Activity of Natural Killer Cells

Abstract The cytotoxic activity of natural killer (NK) cells is regulated by many chemical and physical cues, whose integration mechanism is still obscure. Here, a multifunctional platform is engineered for NK cell stimulation, to study the effect of the signal integration and spatial heterogeneity on NK cell function. The platform is based on nanowires, whose mechanical compliance and site‐selective tip functionalization with antigens produce the physical and chemical stimuli, respectively. The nanowires are confined to micron‐sized islands, which induce a splitting of the NK cells into two subpopulations with distinct morphologies and immune responses: NK cells atop the nanowire islands display symmetrical spreading and enhanced activation, whereas cells lying in the straits between the islands develop elongated profiles and show lower activation levels. The demonstrated tunability of NK cell cytotoxicity provides an important insight into the mechanism of their immune function and introduces a novel technological route for the ex vivo shaping of cytotoxic lymphocytes in immunotherapy.