DNA with a twist and a pinch of salt

In a collaboration with computational biophysicists from the Max Planck Institute of Biophysics, the results were compared to extensive molecular dynamics simulations and help to improve simulations and modeling of DNA structures in biology and nanotechnology.

DNA stores our genetic information and is used in a large range of biotechnological applications. One of the most iconic properties of DNA is its double helical structure, famously discovered by Watson and Crick. However, the structure of DNA also depends on its environment. In particular, since the sugar-phosphate backbone of DNA is highly negatively charged, the concentration and identity of positively charged ions surrounding the DNA will modulate its properties.

A group of researchers led by post doc Willem Vanderlinden and Professor Jan Lipfert has used magnetic tweezers, a high-resolution single-molecule technique, to accurately determine the twist of DNA as a function of ionic conditions. The researchers systematically studied the ions of the alkali and alkaline earth metals, i.e. first and second column of the periodic table. They found that the DNA twist increases with increasing ion concentration, in agreement with the scaling predicted from classic Debye-Hückel electrostatics theory.

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However, the data also revealed an important influence of the ion type. For example, Li+ overwinds DNA more strongly than Na+ (table salt) or K+ (the dominant ion in the cell). To rationalize these trends, the researcher teamed up with Sergio Cruz-León and Nadine Schwierz from the Max Planck Institute of Biophysics in Frankfurt, who performed extensive molecular dynamics simulations. The simulations reveal how different ions localize to different region nears the DNA and how chemical interactions of the ions play an important role in addition to electrostatics.

The direct and quantitative comparison between simulation and experiments reveals strengths, but also limitations of current simulation parameters and provides clues on how to improve them. An exact and quantitative knowledge of how DNA structure depends on its environment will help to better understand its biological roles and to improve the design of DNA-based nano-structures.

Sergio Cruz-León†, Willem Vanderlinden†, Peter Müller, Tobias Forster, Georgina Staudt, Yi-Yun Lin, Jan Lipfert*, and Nadine Schwierz*
Twisting DNA by Salt
Nucleic Acids Res. (2022)
https://doi.org/10.1093/nar/gkac445
(†Authors contributed equally; *Joint corresponding authorship)