Formation and Nanomechanical Properties of Silver-Mediated Guanine DNA Duplexes in Aqueous Solution

Eshana Bethur; Rweetuparna Guha; Ziqian Zhao; Benjamin B Katz; Paul D Ashby; Hongbo Zeng; Stacy M Copp

doi:10.1021/acsnano.3c08008

Formation and Nanomechanical Properties of Silver-Mediated Guanine DNA Duplexes in Aqueous Solution

ACS Nano. 2024 Jan 30;18(4):3002-3010. doi: 10.1021/acsnano.3c08008. Epub 2024 Jan 16.

Authors

Eshana Bethur¹, Rweetuparna Guha¹, Ziqian Zhao², Benjamin B Katz³, Paul D Ashby⁴, Hongbo Zeng², Stacy M Copp^{1

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Affiliations

¹ Department of Materials Science and Engineering, University of California, Irvine, California 92697, United States.
² Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 1H9, Canada.
³ Department of Chemistry, University of California, Irvine, California 92697, United States.
⁴ Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
⁵ Department of Physics and Astronomy, University of California, Irvine, California 92697, United States.
⁶ Department of Chemical and Biomolecular Engineering, University of California, Irvine, California 92697, United States.

Abstract

Silver cations can mediate base pairing of guanine (G) DNA oligomers, yielding linear parallel G-Ag⁺-G duplexes with enhanced stabilities compared to those of canonical DNA duplexes. To enable their use in programmable DNA nanotechnologies, it is critical to understand solution-state formation and the nanomechanical stiffness of G-Ag⁺-G duplexes. Using temperature-controlled circular dichroism (CD) spectroscopy, we find that heating mixtures of G oligomers and silver salt above 50 °C fully destabilizes G-quadruplex structures and converts oligomers to G-Ag⁺-G duplexes. Electrospray ionization mass spectrometry supports that G-Ag⁺-G duplexes form at stoichiometries of 1 Ag⁺ per base pair, and CD spectroscopy suggests that as the Ag⁺/base stoichiometry increases further, G-Ag⁺-G duplexes undergo additional morphological changes. Using liquid-phase atomic force microscopy, we find that this excess Ag⁺ enables assembly of long fiberlike structures with ∼2.5 nm heights equivalent to a single DNA duplex but with lengths that far exceed a single duplex. Finally, using the conditions established to form single G-Ag⁺-G duplexes, we use a surface forces apparatus (SFA) to compare the solution-phase stiffness of single G-Ag⁺-G duplexes with dG-dC Watson-Crick-Franklin duplexes. SFA shows that G-Ag⁺-G duplexes are 1.3 times stiffer than dG-dC duplexes, confirming gas-phase ion mobility spectrometry measurements and computational predictions. These findings may guide the development of structural DNA nanotechnologies that rely on silver-mediated base pairing.

Keywords: DNA nanotechnology; circular dichroism; metal-mediated base pairing; nucleic acids; silver; surface forces apparatus.

MeSH terms

Base Pairing
DNA / chemistry
Guanine* / chemistry
Nucleic Acid Conformation
Silver* / chemistry
Temperature

Substances

Guanine
Silver
DNA