DNA-DNA interactions in tight supercoils are described by a small effective charge density

Christopher Maffeo, Robert Schöpflin, Hergen Brutzer, René Stehr, Aleksei Aksimentiev, Gero Wedemann, and Ralf Seidel
Phys Rev Lett 105(15) 158101 (2010)
DOI:10.1103/PhysRevLett.105.158101   PMID:21230940  BibTex


DNA is so famously known as the carrier of genetic information that the structural and dynamical aspects of the molecule are often neglected. However, most cellular processes that involve DNA cannot be understood without consideration of its interactions with other DNA and proteins. Such interactions can give rise self-assembled structures, for example DNA supercoils, which we strive to understand using a bottom-up approach by examining the most basic constituents of a larger more complex system. Thus, in collaboration with the groups of Ralf Seidel at the University of Technology in Dresden and Gero Wedemann at the University of Applied Sciences Stralsund, we have examined the interactions between DNA helices in plectonemic supercoils using magnetic tweezers, coarse-grained Monte Carlo and atomistic molecular dynamics simulations. Building on our previous work, our group characterized the effective forces between parallel DNA in monovalent electrolytes at different ion concentrations. Our simulations revealed that the force between the DNA molecules is much smaller than that predicted by the Debye-Hückel cylinder model and that continuum models fail to describe DNA electrostatics. We further demonstrate that DNA-DNA interactions in monovalent electrolyte are well described using this simple cylinder model provided a significant charge adaptation factor is employed. Application of this model in coarse-grained Monte Carlo simulations provided results in excellent agreement with experimentally obtained results over a wide range of concentrations. This work is described in a report that appeared in Physical Review Letters.


DNA-DNA interactions are important for genome compaction and transcription regulation. In studies of such complex processes, DNA is often modeled as a homogeneously charged cylinder and its electrostatic interactions are calculated within the framework of the Poisson-Boltzmann equation. Commonly, a charge adaptation factor is used to address limitations of this theoretical approach. Despite considerable theoretical and experimental efforts, a rigorous quantitative assessment of this parameter is lacking. Here, we comprehensively characterized DNA-DNA interactions in the presence of monovalent ions by analyzing the supercoiling behavior of single DNA molecules held under constant tension. Both a theoretical model and coarse-grained simulations of this process revealed a surprisingly small effective DNA charge of 40% of the nominal charge density, which was additionally supported by all-atom molecular dynamics simulations.