DNA in living cells is not just a passive archive of genetic information — it is constantly twisted, coiled, and manipulated by enzymes. One such enzyme, gyrase, introduces excess coiling (supercoiling) into circular DNA molecules called plasmids. In equilibrium, more supercoiling means faster-moving DNA: the tightly coiled rings are compact and slide past each other more easily. Now, a team of researchers at the University of Vienna has shown that when supercoiling is induced rapidly — far from equilibrium — the opposite happens. The DNA slows down dramatically, becoming trapped in a long-lived, glass-like state.
The results, published in the journal ACS Nano, emerge from large-scale molecular simulations led by Jan Smrek at the Computational and Soft Matter Physics Group at the University of Vienna. Roman Staňo carried out a substantial part of the computational work during his time in Vienna before moving to the University of Cambridge, and the study also involved collaborators from the Slovak Academy of Sciences. "We started from the known equilibrium result that more supercoiling speeds up the DNA," explains Jan Smrek, University Assistant at the Faculty of Physics, University of Vienna, and corresponding author of the study. "What surprised us is that when the enzyme acts quickly — before the DNA has time to reorganise — the outcome is completely inverted."
Threads locked in place
In a semi-dilute solution, ring-shaped DNA molecules are not isolated: they thread through each other like links in a loosely woven fabric. Under equilibrium conditions, supercoiling tightens and compacts each ring, reducing these threading entanglements and allowing the DNA to move freely.
But when the supercoiling agent acts faster than the DNA can relax, the rings do not have time to withdraw from their mutual entanglements before becoming tightly coiled. The result is that pre-existing threadings become locked in place. At the same time, rapid coiling creates highly branched molecular conformations — structures with multiple arms — that are geometrically unable to slide out of the threading constraints. The combination of locked threadings and branched conformations causes the system to slow down markedly and enter a state that resembles a topological glass: a material arrested not by low temperature, but by the topology of its molecular architecture.
From biology to functional materials
The study was motivated in part by the biology of DNA supercoiling, but in typical cellular conditions gyrase operates slowly enough for the DNA to relax, placing biological systems outside the regime studied here. The more direct implications lie in materials design. The study suggests a strategy for creating driven, active soft materials whose mechanical properties — specifically their viscosity and relaxation time — can be tuned by controlling the rate at which supercoiling is applied. A slow supercoiling rate leaves the system near equilibrium and relatively fluid; a fast rate locks in the entanglements and vitrifies the material. "This can be a method to create a class of driven materials that become glassy precisely because of the activity, not despite it," says Jan Smrek.
Key findings:
- Rapidly induced supercoiling in circular DNA (plasmid) solutions causes the DNA to slow down — the opposite of what equilibrium supercoiling does.
- The mechanism involves two effects: pre-existing threading entanglements become locked in place by the tightly coiled conformations, and the branched structures formed during fast supercoiling restrict the molecular relaxation pathways.
- The slowdown is stronger for higher applied active torques, even though higher torques also cause faster disintegration of the threading network — a counterintuitive result explained by the induced branching.
- The results open a route to designing active soft materials whose dynamics can be controlled by the rate of an applied enzymatic or mechanical process.Link to paper
Roman Staňo, Renáta Rusková, Dušan Račko, Jan Smrek (2026). Actively Induced Supercoiling Can Slow Down Plasmid Solutions by Trapping the Threading Entanglements. ACS Nano. https://doi.org/10.1021/acsnano.5c10811
Academic contact:
Jan Smrek, University Assistant Computational and Soft Matter Physics Group Faculty of Physics, University of Vienna Boltzmanngasse 5, 1090 Vienna, Austria jan.smrek@univie.ac.at
