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

Angew Chem Int Ed Engl. 2021 Aug 9;60(33):18044-18050. doi: 10.1002/anie.202102206. Epub 2021 Jun 28.

Abstract

Mechanotransduction, the interplay between physical and chemical signaling, plays vital roles in many biological processes. The state-of-the-art techniques to quantify cell forces employ deformable polymer films or molecular probes tethered to glass substrates. However, the applications of these assays in fundamental and clinical research are restricted by the planar geometry and low throughput of microscopy readout. Herein, we develop a DNA-based microparticle tension sensor, which features a spherical surface and thus allows for investigation of mechanotransduction at curved interfaces. The micron-scale of μTS enables flow cytometry readout, which is rapid and high throughput. We applied the method to map and measure T-cell receptor 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.

Keywords: DNA nanotechnology; drug screening; high-throughput quantification; mechanotransduction; molecular tension sensors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / pharmacology
  • Amides / pharmacology
  • DNA / chemistry
  • DNA / metabolism*
  • Dose-Response Relationship, Drug
  • High-Throughput Screening Assays*
  • Humans
  • Mechanotransduction, Cellular / drug effects
  • Optical Imaging
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Pyridines / pharmacology

Substances

  • Amides
  • Platelet Aggregation Inhibitors
  • Pyridines
  • Y 27632
  • DNA
  • Actomyosin