DNA-based microparticle tension sensors (µTS) for measuring cell mechanics in non-planar geometries and for high-throughput quantification.

Abstract

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.