In a groundbreaking study from the University of Cambridge, researchers have revealed a pivotal discovery about DNA behavior as it traverses nanoscale pores—a process crucial to biological functions and emerging DNA sensing technologies. The central focus of this revelation is on plectonemes, structural features of DNA characterized by twisting around itself, which holds significant implications for both biosensing and genomic applications.
For years, scientists believed that when DNA passed through nanopores, the complex electrical signals produced were due to knot formations, similar to pulling a tangled shoelace through a narrow aperture. However, as detailed in a study published in Physical Review X, it is now apparent that these signals are often due to the formation of plectonemes rather than knots. Unlike temporary knots, plectonemes arise from a twisting motion of DNA, powered by electroosmotic flow within the nanopore. This flow creates torque, coiling the DNA into stable, long-lasting structures.
Lead researcher Dr. Fei Zheng and the team found that DNA unwinds into plectonemes under the influence of ionic flow inside the nanopore, producing distinct and enduring electrical signals, unlike the fleeting signatures of knots. The experiments conducted with glass and silicon nitride nanopores demonstrated that the occurrence of these twisted formations increases with both voltage and DNA length. This suggests an unrecognized mechanism at play, corroborated by simulations showing that plectonemes result from torque induced by the nanopore’s electroosmotic flow.
In a novel approach, the researchers engineered ‘nicked’ DNA, which prevents twist propagation, effectively reducing plectoneme formation and validating their structural significance. This advancement enables differentiation between knots and plectonemes based on signal duration, offering new insights into DNA organization and potential damage.
The study’s implications extend beyond fundamental biophysics into practical applications: understanding DNA entanglements within cells, detecting DNA damage associated with diseases, and developing next-generation biosensors become more attainable. The research underscores nanopores not only as precise genetic sensors but also as innovative tools for biopolymer manipulation.
In conclusion, this study uncovers a hidden mechanism of DNA behavior during nanopore translocation, highlighting the central role of plectonemes. This discovery paves the way for advancements in genomic integrity assessments and the creation of enhanced biosensing technologies, demonstrating the untapped potential of nanopore technology in the field of molecular biology.