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Friday, 21 October, 2016

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

Philipp C. Nickels, Bettina Wünsch, Phil Holzmeister, Wooli Bae, Luisa M. Kneer, Dina Grohmann, Philip Tinnefeld, Tim Liedl -
Science, Vol 354, Issue 6310 (2016)

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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