Sensing force and charge at the nanoscale with a single-molecule tether

TL;DR

This paper introduces a high-precision, parallelized single-molecule force and charge sensor using tethered DNA and nanoparticle tracking, enabling detailed analysis of biomolecular charge and force dynamics.

Contribution

The study presents a novel, high-throughput method for measuring nanoscale forces and charges on single molecules with nanometre and microsecond resolution.

Findings

Detects sub-piconewton electrophoretic forces

Identifies charge state changes due to biomolecular interactions

Enables real-time analysis of molecular charge and force dynamics

Abstract

Measuring the electrophoretic mobility of molecules is a powerful experimental approach for investigating biomolecular processes. A frequent challenge in the context of single-particle measurements is throughput, limiting the obtainable statistics. Here, we present a molecular force sensor and charge detector based on parallelised imaging and tracking of tethered double-stranded DNA functionalised with charged nanoparticles interacting with an externally applied electric field. Tracking the position of the tethered particle with simultaneous nanometre precision and microsecond temporal resolution allows us to detect and quantify electrophoretic forces down to the sub-piconewton scale. Furthermore, we demonstrate that this approach is capable of detecting changes to the particle charge state, as induced by the addition of charged biomolecules or changes to pH. Our approach provides an alternative route to studying structural and charge dynamics at the single-molecule level.