When DNA passes through a nanopore — a hole barely wider than the molecule itself — the electrical signal sometimes shows irregular spikes. For decades, researchers interpreted these spikes as knots: the DNA strand tangling as it threads through, like a shoelace pulled through a buttonhole. The knot model shaped how nanopore sequencing data was analyzed, how error rates were estimated, and how the technology was optimized.
Published in Physical Review X, Fei Zheng, Ulrich Keyser, and colleagues at the University of Cambridge showed that the spikes are not knots. They are plectonemes — twisted coils resembling a phone cord, formed because the electric field inside the nanopore drives ionic flow that spins the helical DNA molecule. The torque propagates along the strand, causing sections outside the pore to wind into supercoiled loops. Unlike knots, which tighten under tension and disappear quickly, plectonemes grow larger and persist throughout the entire translocation. They occur far more frequently than knot theory predicted, especially at higher voltages and with longer DNA strands.
The structural insight is about how a good-enough explanation prevents the correct one from being found. The knot model was plausible. It explained the irregular signals. It was consistent with the physics of threading a flexible polymer through a narrow aperture. The problem was not that it was obviously wrong — it was that it was subtly wrong in ways that matched observation well enough to survive without challenge. The signal irregularities looked like knots should look, so they were called knots. The actual mechanism — electroosmotic torque creating plectonemes — produces similar but not identical signatures. The difference was there in the data for decades. It required someone to test whether nicking the DNA (removing the twist) eliminated the spikes. It did. The twist, not the tangle, was the source.