Topological Tuning of DNA Mobility in Entangled Solutions of Supercoiled Plasmids

Abstract

DNA is increasingly employed for bio and nanotechnology thanks to its exquisite versatility and designability. Most of its use is limited to linearised and torsionally relaxed DNA but non-trivial architectures and torsionally constrained – or supercoiled – DNA plasmids are largely neglected; this is partly due to the limited understanding of how supercoiling affects the rheology of entangled DNA. To address this open question we perform large scale Molecular Dynamics (MD) simulations of entangled solutions of DNA plasmids modelled as twistable chains. We discover that, contrarily to what generally assumed in the literature, larger supercoiling increases the average size of plasmids in the entangled regime. At the same time, we discover that this is accompanied by an unexpected increase of diffusivity. We explain our findings as due to a decrease in inter-plasmids threadings and entanglements.

Rheology and Viscoelasticity of Proteins and Nucleic Acids Condensates

“…[92][93][94] This technique is particularly well suited for particles that are too small to be resolved with optical microscopy or to measure the dynamics of fluorescently labelled molecules such as small DNA plasmids. 95…”

Topological digestion drives time-varying rheology of entangled DNA fluids

“…The inset shows the same system in the simulation periodic box and a single uncut plasmid. b,c M SD of the centre of mass of the chains divided by lag-time, g3(t)/t and plotted against lag-time t for varying fractions of cut DNA (serving as a proxy for digestion time) for (b) dense (volume fraction φ = 4% or φ/φ * 16 with φ * = 0.26% [18]) and (c) semi-dilute (volume fraction φ = 0.24% φ * ) regimes. M SDs and lag-time are in simulation units equivalent to σ 2 = 6.25 nm 2 and τB 0.03µs (see SI).…”

“…At odds with recent works on blends of linear and ring polymers [19,26], our results suggest that thickening is monotonic with the fraction of linear chains. To understand this effect, we perform Brownian Dynamics simulations of twistable chains [18,36] modelling 6 kbp plasmids at volume fractions φ = 4% and supercoiling degree σ = 0.06 [18] (see SI for details). We simulate the digestion by linearising a fraction f = 0, 10, 50, 90 and 100% of the chains to mimic different time points during digestion.…”

“…Far less understood are the rheological properties of supercoiled polymers, for which DNA is an archetypal example [12]. Previous microrheology studies on semidilute blends of ring and supercoiled DNA have shown that blends exhibit entanglement dynamics at concentrations well below that needed for monodisperse systems of ring or linear polymers to exhibit similar viscoelastic properties [41].…”

“…At the same time, DNA has been extensively employed to study the physics of polymers in ring [13][14][15][16][17], supercoiled [18,19] and linear topologies [20][21][22][23]. In equilibrium, solutions of concentrated ring polymers exhibit lower viscosity than their linear counterparts [17,20,24,25], while blends of ring and linear polymers exhibit higher viscosity than pure linear chains [19,25,26].…”