function of cells. [8] These forces have different origins, such as actin dynamics, [9] and play important roles at different stages of the lymphocyte immune activity. Initial sampling of antigens on the surface of antigen presenting cells (APCs), as well as activation of immunoreceptors, strongly depends on actin polymerization and dynamics. [10] Moreover, immunoreceptors recognize antigens under mechanical load to discriminate between high-affinity and low-affinity antigens. [11] Once activated, the receptor-antigen complexes on the lymphocyte-APC interface are driven by retrograde actin flow and myosin contraction into highly regulated structures termed immune synapse, whose forces affect the inside-out signaling of lymphocytes. Today, mechanical forces in immune system are a subject of emerging research, which has so far mostly focused on T cells and B cells. [12,13] Studying mechanical forces in cells is challenging, because these forces have relatively low magnitude -mostly at the nanoNewton scale, and often span over miniature regions sized down to the molecular scale. Existing tools include optical traps, [14,15] micropipettes, [16] and atomic force microscopy (AFM), [17,18] which, however, apply and detect forces only at single point on the cell membrane, and do not overview the mechanical behavior of the entire cell. Alternatively, traction force microscopy, which determines the displacement of microbeads embedded in hydrogel surface for cell spreading, maps forces of entire cells, [19][20][21] however, it can hardly detect the exact bead movement since the beads are distributed randomly, and their resting position is unknown. Furthermore, analysis of bead movement requires complex force calculations based on elasticity theory. [22] These constrains can be overcome by elastomeric micropillars for cell spreading, which allow facile mapping of force distribution within cells. [23] Furthermore, micropillars can be functionalized with biomolecules that yield chemical stimuli for various cell functions, such as adhesion [24,25] or immune response, [26] and thereby allow integration of mechanical and biochemical cues. However, the advantages of elastic micropillars come at the expense of their spatial and mechanical resolution. Indeed, poly(dimethyl siloxane) (PDMS) -material of choice for micropillar fabrication -is limited for the fabrication of pillars with micrometerscale size and aspect ratio of 3:1, for which sensing forces below Cells sense their environment by transducing mechanical stimuli into biochemical signals. Commonly used tools to study cell mechanosensing provide limited spatial and force resolution. Here, a novel nanowire-based platform for monitoring cell forces is reported. Nanowires are functionalized with ligands for cell immunoreceptors, and they are used to explore the mechanosensitivity of natural killer (NK) cells. In particular, it is found that NK cells apply centripetal forces to nanowires, and that the nanowires stimulate cell contraction. Based on the nanowire deformation, it is...

NK cells recognize cancer and viral cells by binding their activating receptors to antigens presenting on the membrane of target cells. Although the activation mechanism of NK cells is a subject of extensive research today, the role of the composition and spatial distribution of activating ligands in NK cell cytotoxicity is barely understood. In this work, we engineered a nanochip whose surface was patterned with matrices of antigens for NKG2D activating receptors. These matrices mimicked the spatial order of the surface of antigen presenting cells with molecular resolution. Using this chip, we elucidated the effect of the antigen spatial distribution on the NK cell spreading and immune activation. We found that the spatial distribution of the ligand within the 100 nm length-scale provides the minimal conditions for NKG2D regulated cell spreading. Furthermore, we found that the immune activation of NK cells requires the same minimal spatial distribution of activating ligands. Above this threshold, both spreading and activation plateaued, confirming that these two cell functions work hand in hand. Our study provides an important insight on the spatial mechanism of the cytotoxic activity of NK cells. This insight opens the way to rationally designed antitumor therapies that harness NK cytotoxicity.