Unzipping of knotted DNA via nanopore translocation

TL;DR

This study uses molecular dynamics simulations to explore how knotted DNA affects nanopore unzipping, revealing that knots slow down unzipping at high forces due to topological and entanglement friction, with implications for biological and experimental contexts.

Contribution

It provides the first detailed analysis of how DNA knots influence nanopore unzipping dynamics, highlighting the roles of topological friction and entanglement.

Findings

Knots do not significantly affect unzipping at low forces.

Knotted DNA unzips more slowly and heterogeneously at high forces.

Friction from topological constraints and entanglement hinders unzipping.

Abstract

DNA unzipping by nanopore translocation has implications in diverse contexts, from polymer physics to single-molecule manipulation to DNA-enzyme interactions in biological systems. Here we use molecular dynamics simulations and a coarse-grained model of DNA to address the nanopore unzipping of DNA filaments that are knotted. This previously unaddressed problem is motivated by the fact that DNA knots inevitably occur in isolated equilibrated filaments and in vivo. We study how different types of tight knots in the DNA segment just outside the pore impact unzipping at different driving forces. We establish three main results. First, knots do not significantly affect the unzipping process at low forces. However, knotted DNAs unzip more slowly and heterogeneously than unknotted ones at high forces. Finally, we observe that the microscopic origin of the hindrance typically involves two concurrent causes: the topological friction of the DNA chain sliding along its knotted contour and the additional friction originating from the entanglement with the newly unzipped DNA. The results reveal a previously unsuspected complexity of the interplay of DNA topology and unzipping, which should be relevant for interpreting nanopore-based single-molecule unzipping experiments and improving the modeling of DNA transactions in vivo.