Nanopore Force Spectroscopy: Insights from Molecular Dynamics Simulations - Nanopores: Sensing and Fundamental Biological Interactions - page 351

DVQ=a [ 14 , 15 , 28 ], which was attributed to the effect of the DNA's counterions.
In a hybrid setup, employing both a nanopore and optical tweezers, Keyser et al. [ 28 ]
obtained an effective charge Q eff ¼ 0.05 e , which is about 25% of the

bare charge value, for DNA held fixed in pores having diameters from 6 to 11 nm.
What is the physical mechanism responsible for the reduction of the force from
the bare electrostatic value of

0.50

DVQ=a ? One could propose that a certain number of
counterions bind to the DNA, which results in an effective reduction of the charge.
Is this simple proposal correct? Keyser et al. [ 28 ] noted the “complex interplay
between hydrodynamics and electrical charges in the screening layer of DNA.”
A theoretical description subsequently developed by Ghosal [ 61 ] highlighted the
importance of electro-osmotic flow. If flow of the electrolyte solution is indeed
important for determining the force on the DNA, how might this force depend on
the properties of the nanopore?
Luan and Aksimentiev [ 62 ] used MD to calculate the force on DNA in a
nanopore and determine the contribution of electro-osmotic flow to this force.
Figure 14.6a illustrates the protocol used in the simulations. A virtual spring
holds the DNA, while the DNA is subject to electrostatic force as well as that due
to electro-osmotic flow; the force on the DNA can be calculated from the extension
of the spring. Under an external field, K + and Cl ions in the nanochannel move in
opposite directions; however, the K + counterions outnumber the Cl ions within
3.0 nm of the axis of the DNA, and therefore, induce a net flow of solution near the
DNA. This flow moves in the direction opposite to the direction that the DNA
would move if not restrained, exerting a viscous drag on the DNA and reducing the
magnitude of the force on the DNA from its bare electrostatic value

DVQ=a .

Fig. 14.6 Electro-osmotic flow in the vicinity of dsDNA. (a) Snapshot from MD simulation of
effectively infinite DNA placed in an effectively infinite nanochannel. The center of mass of the
DNA is attached to virtual spring to stall its motion under the force F z , which results from external
electric field E z and the electro-osmotic flow due to ions in the pore. (b) Velocity of the electro-
osmotic flow vs. distance from the DNA's axis in various nanochannels. Diamonds , triangles , and
circles pertain to an atomically smooth channel having a diameter of 6.0 nm, a corrugated channel
having a diameter of 6.0 nm, and an atomically smooth channel having a diameter of 4.5 nm,
respectively. Figure adapted from [ 62 ]