Superresolved microparticle traction force microscopy reveals subcellular force patterns in immune cell-target interactions

Force exertion is an integral part of cellular behavior. Traction force microscopy (TFM) has been instrumental for studying such forces, providing both spatial and directional force measurements at subcellular resolution. However, the applications of classical TFM are restricted by the typical planar geometry. Here, we develop a particle-based force sensing strategy, specifically designed for studying ligand-dependent cellular interactions. We establish an accessible batch approach for synthesizing highly uniform, deformable and tunable hydrogel particles. In addition, they can be easily derivatized to trigger specific cellular behavior. The 3D shape of such particles can be resolved with superresolution (< 50 nm) accuracy using conventional confocal microscopy. We introduce a computational method that allows us to infer surface traction forces with high sensitivity (~ 10 Pa), directly from the particle shape without embedding tracers in the particle. We illustrate the potential and flexibility of this approach by measuring forces throughout phagocytic engulfment. This strategy can readily be adapted for studying cellular forces in a wide range of applications.