Conformations and cryo-force spectroscopy of spray-deposited single-strand DNA on gold

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 N m −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 longA.B., A.H., and E.M. and R.P., T.G., and T.M. thank the Swiss National Science Foundation (SNF) and the Swiss Nanoscience Institute (SNI). The COST Action MP1303 is gratefully acknowledged. Ru. P. and J.G.V. thank the financial support of the Spanish MINECO (projects MAT2014-54484-P, MDM-2014-0377, and MAT2017-83273-R) and also the computer resources, technical expertise, and assistance provided by the Red Española de Supercomputación at the Minotauro Supercomputer (BSC, Barcelona). J.G. V. acknowledges funding from a Marie Sklodowska-Curie Fellowship within the Horizons 2020 framework. Dr. Marcin Kisiel is acknowledged for fruitful discussio