Electro-osmotic screening of the DNA charge in a nanopore
Original entry: Darren Yang, AP225, Fall 2010
Electro-osmotic screening of the DNA charge in a nanopore B. Luan & A. Aksimentiev, Phys. Rev. E, 78, (2008)
The authors used molecular dynamics simulations to characterize the microscopic origin of the force experienced by DNA in a bulk electrolyte and a solid-state nanopore when subject to an external electrostatic field E. They found that effective screening of the DNA charge was originate from the hydrodynamic drag of the electro-osmotic flow that is driven by the motion of counterions along the surface of DNA. In addition, they show that the effective driving force F in a nanopore obeys the same law as in a bulk electrolyte. Thus, they suggested that by utilizing this relationship a new method to for determining the effective driving force on DNA in a nanopore, that does not require a direct force measurement, could be developed.
In recent years, the technology of DNA molecules translocation through nanopores driven by electric field holds a great promise for genome sequencing and high-throughput single molecule force spectroscopy. Characterization of the force experienced by DNA in a nanopore is critical to understanding the microscopic mechanics of the DNA transport; however, the interpretation of these measurements has been ambiguous. Previously, it has been shown that of hydrodynamic interactions between DNA and the solvent inside a solid-state nanopore plays a significant role. Thus, in this paper the author aimed to demonstrate that the effective screening of the DNA charge is caused by the electro-osmotic flow that develops near the DNA surface and driven by the motion of counterions.
Two systems were studied: (1) a DNA fragment submerged in a bulk electrolyte (Figure 1A). (2) a DNA fragment in a cylindrical channel that is used as a model of a solid-state nanopore (Figure 1B). The authors simulate the response of the DNA and electrolyte to the applied electric field, and measure directly the stall force that is required to stop the DNA motion and balance the effective driving force.
The authors measured the forces require to stop the DNA drift in different magnitude of electric fields. The DNA initially drifts opposite the field direction, increasing the force of the spring on the DNA. Eventually, the spring force balances the effective driving force and the DNA motion stops. The stall force measured thereby depends on the magnitude of the external electric field (Figure 2A). The plot of the stall force versus the total force of the external electric field on bare DNA (Figure 2B) reveals a linear dependence with a slope of 0.243.
Figure 1. (a) DNA helix in a water box. (b) DNA helix in a solid-state nanopore. In both systems, a uniform external electric field E is applied to all atoms, whereas a harmonic spring force F is applied to DNA only. Ions K+ and Cl− are shown as spheres.
Next they look the radial distribution of ions around DNA (Figure 2C), which does not depend on the strength of the external electric field. The density of potassium ions has a maximum inside the major groove of the DNA helix (the peak at r=5 Å is caused by strong interaction between potassium ions and nitrogen atoms of the adenine bases) and near the phosphate groups of the DNA backbone (the peak around r=12 Å arises from a cloud of potassium ions attracted to the negatively charged phosphate groups of the DNA backbone). The author also found that ions are not bound to DNA because the average residence time of potassium ions at the DNA surface was found to be just several picoseconds, close to the average residence time of water. The velocity profile of water as a function of the radial distance from the center of the DNA helix is shown in Figure 2D. The water velocity reaches a maximum at about 22 Å. The maximum velocity increases with the strength of the applied electric field. Clearly, the stall force depends on the electro-osmotic flow and thus on the friction between DNA and the flow.
Figure 2. (a) Stall force F versus simulation time at various strengths of the external electric fields. (b) Stall force versus total electric force on bare DNA. (c) Ion density versus distance from the DNA central axis. (d) Velocity of the electro-osmotic flow versus distance from the DNA central axis.