DNA‐Based Microparticle Tension Sensors (μTS) for Measuring Cell Mechanics in Non‐planar Geometries and for High‐Throughput Quantification

Mechanotransduction, the interplay between physical and chemical signaling, plays vital roles in many biological processes ranging from cell differentiation to metastasis. The state-of-the-art techniques to quantify cell forces employ deformable polymer films or molecular probes tethered to glass substrates. These types of flat substrates limit applications in investigating mechanotransduction on non-planar geometries where physiological activities such as phagocytosis and immunological synapse formation mostly occur. A second challenge is the low throughput of microscopy readout which limits the application of current assays in fundamental and clinical research. We address these challenges by developing a DNA-based microparticle tension sensor (μTS), which features a spherical surface and thus allows for investigation of mechanical events at curved interfaces or within groups of cells in suspension. Importantly, the micron-scale of μTS enables flow cytometry readout, which is rapid and high throughput. To demonstrate the scope of μTS, we applied the method to map and measure T-cell receptor (TCR) forces and platelet integrin forces at 12 and 56 pN thresholds. Furthermore, we quantified the inhibition efficiency of two anti-platelet drugs providing a proof-of-concept demonstration of μTS to screen drugs that modulate cellular mechanics.