Water-Compression Gating of Nanopore Transport

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Water-Compression Gating of Nanopore Transport

James Wilson and Aleksei Aksimentiev

Phys. Rev. Lett. 120, 268101 – Published 26 June 2018

Abstract

Electric field-driven motion of biomolecules is a process essential to many analytics methods, in particular, to nanopore sensing, where a transient reduction of nanopore ionic current indicates the passage of a biomolecule through the nanopore. However, before any molecule can be examined by a nanopore, the molecule must first enter the nanopore from the solution. Previously, the rate of capture by a nanopore was found to increase with the strength of the applied electric field. Here, we theoretically show that, in the case of narrow pores in graphene membranes, increasing the strength of the electric field can not only decrease the rate of capture, but also repel biomolecules from the nanopore. As the strong electric field polarizes water near and within the nanopore, the high gradient of the field also produces a strong dielectrophoretic force that compresses the water. The pressure difference caused by the sharp water density gradient produces a hydrostatic force that repels DNA or proteins from the nanopore, preventing, in certain conditions, their capture. We show that such local compression of fluid can regulate the transport of biomolecules through nanoscale passages in the absence of physical gates and sort proteins according to their phosphorylated states.

Received 1 December 2017
Revised 18 April 2018

DOI:https://doi.org/10.1103/PhysRevLett.120.268101

Physics Subject Headings (PhySH)

Electrophoresis Polymer translocation Translocation

Physics of Living SystemsPolymers & Soft Matter

Authors & Affiliations

James Wilson

Department of Physics, University of Illinois at Urbana–Champaign, 1110 West Green Street, Urbana, Illinois 61801, USA

Aleksei Aksimentiev^*

Department of Physics, University of Illinois at Urbana–Champaign, 1110 West Green Street, Urbana, Illinois 61801, USA and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, Illinois 61801, USA

^*aksiment@illinois.edu

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Issue

Vol. 120, Iss. 26 — 29 June 2018

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Images

Figure 1
MD simulation of DNA capture and translocation through a graphene nanopore. (a) Simulation setup. A 16 basepair fragment of double stranded DNA (orange and blue) is placed 8 Å away from a 3.5 nm diameter nanopore in a graphene membrane (dark gray) and submerged in a hexagonal prism volume of 1 M KCl electrolyte (semitransparent surface; ions not shown). Phosphorous atoms of the DNA fragment are restrained to a 1.88 nm diameter cylinder coaxial with the nanopore axis; the DNA is free to move along the cylinder and rotate about its axis. An electric field $E$ is applied normal to the membrane. (b) $Z$ coordinate of the leading base of the DNA fragment in twenty independent MD simulations (each shown using unique color) carried out under a transmembrane bias of 100 mV. The graphene membrane is located at $z = 0$ . Snapshots illustrate the location of the DNA fragment for the highlighted translocation trace (black). For the first 1 ns of each simulation, the $z$ coordinates of the DNA’s phosphorous atoms are restrained to their initial values. (c) The average translocation time versus transmembrane bias, $V$ . Red line shows a $1 / V$ fit. (d) Average capture rate versus transmembrane bias. The average capture rate was computed as the mean of inverse capture times. If a DNA molecule was not captured within 20 ns, the capture time was assumed to be 40 ns, contributing uncertainty to the average capture rate of less than $0.025 {ns}^{- 1}$ . In panels (c) and (d), the error bars indicate the standard error of mean.
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Figure 2
Effective force on DNA. (a) Schematic of MD measurement of the effective force. A DNA molecule is held distance $h$ from the 3.5 nm diameter nanopore in a graphene membrane using harmonic restraints. Steady-state displacement of DNA atoms from their initial coordinates along the nanopore axis reports on the effective force [48]. Each effective force value was determined by averaging over at least three independent simulations each lasting 20 ns. (b) Effective force on DNA held coaxially with a nanopore at different heights relative to the graphene membrane as a function of transmembrane bias; lines are a guide for the eye. Height is defined as the distance between the center of mass of the closest base to the graphene, and the plane of the graphene. The top and bottom insets illustrate systems with $h = - 20$ and $h = + 8 Å$ , respectively. Vertical line at $h = 8 Å$ corresponds to data plotted in panel (c) using blue circles. (c) Effective force versus transmembrane bias for canonical DNA (circles), neutrally charged DNA (squares), horizontally oriented DNA (diamonds), and a theoretical model (stars). All DNA constructs are placed the same distance ( $h = 8 Å$ ) away from the membrane. (d) Water flux through a 3.5 nm nanopore for canonical and neutrally charged DNA held 8 Å away from the graphene membrane, coaxial with the nanopore, as a function of transmembrane bias.
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Figure 3
Dielectrophoretic pressurization of a graphene nanopore. (a) Schematic illustration of pressure build up caused by dielectrophoresis. The arrows indicate the direction and magnitude of the dielectrophoretic force on water molecules. (b) Electric field strength along the pore axis at several transmembrane biases. For each transmembrane bias, data in panels (b)–(d) derive from at least three independent simulations of the open-pore system, each lasting 20 ns. (c) Trajectory-average projection of water dipole moment onto the nanopore axis. (d) Local dielectrophoretic force per water molecule. (e) Map of electrolyte density differential produced by a transmembrane bias. The image shows a cross section of the 3D map obtained by subtracting local electrolyte density maps at 1 and 0 V transmembrane bias; only the region near the nanopore is shown. (f) Local pressure along the nanopore axis. The lines show the pressure values calculated by integration of the force plot [panel (d)]. The bar graph indicates pressure values calculated from the observed changes of water density and the measured water compressibility (Supplemental Material [27], Fig. S12).
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Figure 4
Potential of mean force (PMF) of a villin headpiece protein along the symmetry axis of a 4.9 nm diameter nanopore. The PMF was computed for two phosphorylation states of the protein corresponding to the net charge of one (blue, state P1) and three (green, state P2) electrons. Vertical dashed lines schematically illustrate the location of a graphene membrane; horizontal dashed line indicates a $0 kcal / mol$ value.
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