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Conformations and cryo-force spectroscopy of spray-deposited single-strand DNA on gold
12.02.2019 11:43

Cryo-electron microscopy can determine the structure of biological matter in vitrified liquids. However, structure alone is insufficient to understand the function of native and engineered biomolecules. So far, their mechanical properties have mainly been probed at room temperature using tens of pico-newton forces with a resolution limited by thermal fluctuations. Here we combine force spectroscopy and computer simulations in cryogenic conditions to quantify adhesion and intra-molecular properties of spray-deposited single-strand DNA oligomers on Au(111). Sub-nanometer resolution images reveal folding conformations confirmed by simulations. Lifting shows a decay of the measured stiffness with sharp dips every 0.2-0.3 nm associated with the sequential peeling and detachment of single nucleotides. A stiffness of 30-35 Nm-1 per stretched repeat unit is deduced in the nano-newton range. This combined study suggests how to better control cryo-force spectroscopy of adsorbed heterogeneous (bio)polymer and to potentially enable single-base recognition in DNA strands only few nanometers long.

Publication

Rémy Pawlak, J. G. Vilhena, Antoine Hinaut, Tobias Meier, Thilo Glatzel, Alexis Baratoff, Enrico Gnecco, Rubén Pérez, Ernst Meyer: "Conformations and cryo-force spectroscopy of spray-deposited single-strand DNA on gold". Nature Communications 10 (2019), Article number: 685.


41467_2019_8531_Fig1

Fig. 1: ssDNA morphologies as a function of Au(111) annealing temperature.
(a) Overview of STM images of spray-depo­sited ssDNA on Au(111) at room tempe­rature, after annea­ling at 340, 440, and above 500 K, respec­tively. (b) STM image of hydra­ted ssDNA after spray-depo­sition at room tem­pe­ra­ture. (c) Top view of a repre­sen­ta­tive ssDNA structure on Au(111) obtai­ned from MD simu­lations per­for­med in vacuum at 400 K. (d) STM image of a dehy­drated single 20-cyto­sine ssDNA oligo­mer after 440-K annea­ling and the cor­res­pon­ding high reso­lution con­stant height AFM image, both acqui­red with a CO-termi­nated tip. The struc­tural model of c is super­impo­sed on the STM image. (e) STM image of self-assem­bled dehy­dra­ted ssDNA oligo­mers after 500 K annea­ling and the corres­pon­ding AFM image. All STM images were recorded at 5 K with I = 2 pA and V = -1.3 V. Properly scaled top views of the re­pre­sen­ta­tive ssDNA struc­ture are super­impo­sed on (b), (d), (e) as a guide for the eye.

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