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

Abstract

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

Slow DNA Transport through Nanopores in Hafnium Oxide Membranes

“…Recent Langevin dynamics simulations of a strongly interacting pore find a superexponential relationship between driving force and dwell time, 65 which produce remarkably similar behavior to our experiments. Though further investigation is required, two non-exclusive mechanisms can explain this behavior: (1) the pore we have used is too small to allow unhindered passage of ssDNA nucleobases, resulting in steric-dominated stick–slip motion through the pore, 66 and (2) chemical interactions between ssDNA and the HfO 2 surface are responsible for this observed friction. 61 …”

Stretching and Controlled Motion of Single-Stranded DNA in Locally Heated Solid-State Nanopores

“…Various methods have been applied to slow the translocation of biomolecules through nanopores, 7,8 including optical tweezers, 9 magnetic beads, 10 electrostatic 11–14 and steric 15 traps, and modifications to solvent. 16,17 Despite extensive efforts, a general method providing the desired level of control remains a highly researched subject.…”

Controlling molecular transport through nanopores

“…The molecule has to be denatured during this process and so should yield information about the primary sequence of the molecule [77]. In brief, ionic current measurements in combination with MD simulations show that the translocation time and current depend on the DNA sequence [77]. This is a combination of both primary and secondary structures of DNA.…”