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Investigation of compacted DNA structures induced by Na+ and K+ monovalent cations using biological nanopore

Abstract

In aqueous solutions, an elongated, negatively charged DNA chain can quickly change its conformation into a compacted globule in the presence of positively charged molecules, or cations. This well-known process, called DNA compaction, is a highly potential method for gene therapy and delivery. Experimental conditions to induce these compacted DNA structures are often limited to the use of common compacting agents, such as cationic surfactants, polymers, and multivalent cations. In this study, we show that in highly concentrated buffers of 1M monovalent cation solutions at pH 7.2 and 10, biological nanopores allow real-time sensing of individual compacted structures induced by K+ and Na+, the most abundant monovalent cations in human bodies. Herein, we study the ratio between compacted and linear structures for 15-mer single-stranded DNA molecules containing only cytosine nucleotides, optimizing the probability of linear DNA chains being compacted. Since the binding affinities of each nucleotide to cations is different, the ability of DNA strand to fold into compacted structure depends highly on the type of cations and nucleotides present. Our experimental results are favorably comparable with findings from previous molecular dynamics simulations for DNA compacting potential of K+ and Na+ monovalent cations. We estimate that the majority of single-stranded DNA molecules in our experiment are compacted. From the current traces of nanopores, the ratio of compacted DNA to linear DNA molecules is about 30:1 and 15:1, at a pH of 7.2 and pH of 10 respectively. Our comparative studies reveal that Na+ monovalent cations have a greater potential of compacting the 15C-ssDNA than a K+ cation does.

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Publication details

The article was received on 15 Nov 2017, accepted on 06 Jan 2018 and first published on 09 Jan 2018


Article type: Paper
DOI: 10.1039/C7AN01857F
Citation: Analyst, 2018, Accepted Manuscript
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    Investigation of compacted DNA structures induced by Na+ and K+ monovalent cations using biological nanopore

    T. Vu, S. Davidson and J. Shim, Analyst, 2018, Accepted Manuscript , DOI: 10.1039/C7AN01857F

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