Topological Tuning of DNA Mobility in Entangled Solutions of Supercoiled Plasmids

Abstract

Understanding the behaviour of ring polymers in dense solutions is one of the most intriguing problems in polymer physics with far-reaching implications from material science to genome biology. Thanks to its natural occurrence in circular form, DNA has been intensively employed as a proxy to study the fundamental physics of ring polymers in different topological states. Yet, torsionally constrained – such as supercoiled – topologies have been largely neglected so far. Extreme entanglement and high supercoiling levels are commonly found in the genetic material of both pro- and eukaryotes and, at the same time, the applicability of existing theoretical models to dense supercoiled DNA is unknown. To address this gap, here we couple large scale Molecular Dynamics (MD) simulations of twistable chains together with Differential Dynamic Microscopy (DDM) of entangled supercoiled DNA plasmids. We discover that, strikingly, and contrarily to what is generally assumed in the literature, a higher degree of supercoiling increases the average size of plasmids in entangled solutions. At the same time, we discover that this is accompanied by an unexpected enhancement in DNA mobility. We reconcile these apparently contradicting findings as due to the fact that supercoiling drives highly asymmetric plasmid conformations, decreases inter-plasmids entanglements and, in particular, reduces the number of threadings between DNA rings. Our numerical and experimental results also suggest a way to topologically tune DNA mobility via supercoiling, thus enabling the orthogonal control over the (micro)rheology of DNA-based complex fluids with respect to other traditional methods such as DNA length or concentration.