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Nickels, Philipp C.; Wünsch, Bettina; Holzmeister, Phil; Bae, Wooli; Kneer, Luisa M.; Grohmann, Dina; Tinnefeld, Philip and Liedl, Tim (2016): Molecular force spectroscopy with a DNA origami-based nanoscopic force clamp. In: Science, Vol. 354, No. 6310: pp. 305-307

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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 Frster 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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