Slowing the translocation of double-stranded DNA using a nanopore smaller than thedouble helix

Abstract

It is now possible to slow and trap a single molecule of double-stranded DNA (dsDNA), bystretching it using a nanopore, smaller in diameter than the double helix, in a solid-statemembrane. By applying an electric force larger than the threshold for stretching, dsDNAcan be impelled through the pore. Once a current blockade associated with a translocatingmolecule is detected, the electric field in the pore is switched in an interval less than thetranslocation time to a value below the threshold for stretching. According to moleculardynamics (MD) simulations, this leaves the dsDNA stretched in the pore constriction withthe base-pairs tilted, while the B-form canonical structure is preserved outside the pore.In this configuration, the translocation velocity is substantially reduced from1 bp/10 ns to ∼ 1 bp/2 ms in the extreme, potentially facilitating high fidelity reads for sequencing, precise sorting,and high resolution (force) spectroscopy.