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

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Science  21 Oct 2016:
Vol. 354, Issue 6310, pp. 305-307
DOI: 10.1126/science.aah5974

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Many tiny force sensors

Several techniques can measure forces on biomolecules, but the need to connect the molecule to the macroscopic world often limits the rate at which data can be taken. Nickels et al. created large arrays of nanoscale force sensors by using DNA origami structures. Single-stranded DNA molecules of different lengths attached to the molecule of interest acted as entropic springs, with shorter strands exerting more force. The authors used their setup to study the bending of DNA induced by the TATA-binding protein.

Science, this issue p. 305

Abstract

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.

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