Nanoscale Mechanosensing of Natural Killer Cells is Revealed by Antigen‐Functionalized Nanowires

Abstract 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 calculated that cells apply forces of down to 10 pN, which is the smallest value demonstrated so far by microstructured platforms for cell spreading. Furthermore, the roles of: i) nanowire topography and ii) activating ligands in the cell immune function are studied and it is found that only their combination produces enhanced population of activated NK cells. Thus, a mechanosensing mechanism of NK cells is proposed, by which they integrate biochemical and mechanical stimuli into a decision‐making machinery analogous to the AND logic gate, whose output is the immune activation. This work reveals unprecedented mechanical aspects of NK cell immune function and introduces an innovative nanomaterial for studying cellular mechanics with unparalleled spatial and mechanical resolution.