Topological tuning of DNA mobility in entangled solutions of supercoiled plasmids

Abstract

Ring polymers in dense solutions are among the most intriguing problems in polymer physics. Because of its natural occurrence in circular form, DNA has been extensively used 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. The applicability of existing theoretical models to dense supercoiled DNA is thus unknown. Here, we address this gap by coupling large-scale molecular dynamics simulations with differential dynamic microscopy of entangled supercoiled DNA plasmids. We find that, unexpectedly, larger supercoiling increases the size of entangled plasmids and concomitantly induces an enhancement in DNA mobility. These findings are reconciled as due to supercoiling-driven asymmetric and double-folded plasmid conformations that reduce interplasmid entanglements and threadings. Our results suggest a way to topologically tune DNA mobility via supercoiling, thus enabling topological control over the (micro)rheology of DNA-based complex fluids.

Rheology and Viscoelasticity of Proteins and Nucleic Acids Condensates

“… 92 − 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 labeled probes and molecules, such as small DNA plasmids. 95 …”

Rheology and Viscoelasticity of Proteins and Nucleic Acids Condensates

“…In fact, one can also employ Differential Dynamic Microscopy (DDM), a technique that relies on the spatial and temporal autocorrelation of the pixel intensities in order to extract the dynamics of the particles in the system [87][88][89]. 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 [90].…”

Topological digestion drives time-varying rheology of entangled DNA fluids

“…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 [18,35] 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.…”

“…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].…”