New Study Unties DNA Knot to Improve Sequencing Accuracy
Long DNA molecules can self-entangle into knots. And these knots occur in biological systems to serve the purpose of a model system for polymer entanglement, and affect the efficacy of modern genomics technologies.
Now, researchers at the MIT have, for the first time, discovered factors that determine whether a knot moves along the strand or “jams” in place using a technology that stretches and images these structures.
“People who study polymer physics have suggested that knots might be able to jam, but there haven’t been good model systems to test it,” says Patrick Doyle, the Robert T. Haslam Professor of Chemical Engineering and the senior author of the study. “We showed the same knot could go from being jammed to being mobile along the same molecule. You change conditions and it suddenly stops, and then change them again and it suddenly moves.”
The team designed a unique microfluidic system constituted by a T channel with an electric field that diverges at the top of the T. A DNA molecule located at the top of this T will be pulled equally toward each arm, forcing it to stay in place. Later, the team
discovered that they could well manipulate these knots in pinned DNA molecules by varying the strength of the electric field.In their experiments, the team noticed that when the field is weak, knots tend to move along the molecule toward the closer end. When they reach the end, they unravel. And conversely, when it is strong, the DNA is forced to stretch out fully, causing these knots to jam in.
Dmitrii Makarov, a professor of chemistry at the University of Texas at Austin, who was not involved in the study, describes it as “an elegant experimental demonstration that knots in DNA can ‘jam’ under tension, just like macroscopic knots do in our everyday experience. This work also provides important fundamental insights into friction on molecular scale, a phenomenon that is still poorly understood.”
The researchers, in the future intend to study other phenomena related these knotted proteins, including the process of untying more complex knots as well as the interactions between two knots in a molecule.
