Local structure of DNA toroids reveals curvature-dependent intermolecular forces

Abstract

In viruses and cells, DNA is closely packed and tightly curved thanks to polyvalent cations inducing an effective attraction between its negatively charged filaments. Our understanding of this effective attraction remains very incomplete, partly because experimental data is limited to bulk measurements on large samples of mostly uncurved DNA helices. Here we use cryo electron microscopy to shed light on the interaction between highly curved helices. We find that the spacing between DNA helices in spermine-induced DNA toroidal condensates depends on their location within the torus, consistent with a mathematical model based on the competition between electrostatic interactions and the bending rigidity of DNA. We use our model to infer the characteristics of the interaction potential, and find that its equilibrium spacing strongly depends on the curvature of the filaments. In addition, the interaction is much softer than previously reported in bulk samples using different salt conditions. Beyond viruses and cells, our characterization of the interactions governing DNA-based dense structures could help develop robust designs in DNA nanotechnologies.

Twist-induced local curvature of filaments in DNA toroids

“…In this case, curvature decreases with the distance from the z-axis (Fig. 2A), as in our previous paper [3]. If Ω = 0, twist alters the spatial distribution of curvature.…”

“…Along the direction denoted by e R in Fig. 1, the distance between neighboring filaments decreases with their distance from the z-axis [3]. In the same article, we explain this behavior by means of a simple theory of mechanical equilibrium, based on the competition between local filament-filament interactions and DNA bending rigidity.…”

“…Our prediction in Ref. [3] relies on the assumed distribution of filaments' curvature in the bundle, which neglects twist. However, twist can spatially redistribute curvature within the bundle, possibly invalidating our assumption.…”

“…III, we adapt our model to the case of DNA toroids and assess the validity of the assumption used in Ref. [3].…”

Chromonic liquid crystals and packing configurations of bacteriophage viruses

“…Among the most relevant shortcomings of the proposed model, we mention the fact that the distance, d, between neighbouring DNA segments within the ordered region of the capsid is not constant. In the case of toroidal domains, this has been pointed out in recent work by Barberi et al [25]. Such a distance is also very sensitive to changes in ionic conditions [26].…”