Molecular force spectroscopy with a DNA origami-based nanoscopic force clamp

Science. 2016 Oct 21;354(6310):305-307. doi: 10.1126/science.aah5974.


Forces in biological systems are typically investigated at the single-molecule level with atomic force microscopy or optical and magnetic tweezers, but these techniques suffer from limited data throughput and their requirement for a physical connection to the macroscopic world. We introduce a self-assembled nanoscopic force clamp built from DNA that operates autonomously and allows massive parallelization. Single-stranded DNA sections of an origami structure acted as entropic springs and exerted controlled tension in the low piconewton range on a molecular system, whose conformational transitions were monitored by single-molecule Förster resonance energy transfer. We used the conformer switching of a Holliday junction as a benchmark and studied the TATA-binding protein-induced bending of a DNA duplex under tension. The observed suppression of bending above 10 piconewtons provides further evidence of mechanosensitivity in gene regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Cruciform / chemistry
  • DNA, Cruciform / ultrastructure*
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / ultrastructure*
  • Fluorescence Resonance Energy Transfer / methods*
  • Gene Expression Regulation
  • Nanotechnology / methods
  • Promoter Regions, Genetic
  • Protein Binding
  • Single Molecule Imaging / methods*
  • Stress, Mechanical
  • TATA-Box Binding Protein / chemistry
  • TATA-Box Binding Protein / ultrastructure


  • DNA, Cruciform
  • DNA, Single-Stranded
  • TATA-Box Binding Protein