Nanoscopic Characterization of DNA within Hydrophobic Pores: Thermodynamics and Kinetics

Abstract

The energetic and transport properties of a double-stranded DNA dodecamer encapsulated in hydrophobic carbon nanotubes are probed employing two limiting nanotube diameters, D = 4 nm and D = 3 nm, corresponding to (51,0) and (40,0) zig-zag topologies, respectively. It is observed that the thermodynamically spontaneous encapsulation in the 4 nm nanopore (ΔG ≈ -40 kJ/mol) is annihilated when the solid diameter narrows down to 3 nm, and that the confined DNA termini directly contact the hydrophobic walls with no solvent slab in-between. During the initial moments after confinement (t ≤ 2-3 ns), the biomolecule translocates along the nanopore's inner volume according to Fick's law (∼ t) with a self-diffusion coefficient D = 1.713⋅10 -9 m 2 /s, after which molecular diffusion assumes a single-file type mechanism (∼ t 1/2 ). As expected, diffusion is anisotropic, with the pore main axis as the preferred direction, but an in-depth analysis shows that the instantaneous velocity probabilities are essentially identical along the x, y and z directions. The 3D velocity histogram shows a maximum probability located at <v> = 30.8 m/s, twice the observed velocity for a single-stranded three nucleotide DNA encapsulated in comparable armchair geometries (<v> = 16.7 m/s, D = 1.36-1.89 nm). Because precise physiological conditions (310 K and [NaCl] = 134 mM) are employed throughout, the present study establishes a landmark for the development of next generation in vivo drug delivery technologies based on carbon nanotubes as encapsulation agents.

Diameter Dependent Melting and Softening of dsDNA Under Cylindrical Confinement

“…In the case of a wider SWCNT of diameter 4.07 nm, we can see a slight reduction of the electrostatic energy between the bases of dsDNA after about 150 nanoseconds of simulation time. This is due to the adsorption of the end bases to the wall of the SWCNT, as shown in Figure 8E that leads to a slight unzipping of the end bases as described by Cruz et al ( Cruz et al, 2014 ; Cruz et al, 2015 ) and Nandy et al (2012) .…”

“…SWCNTs are expected to be efficient candidates to be used as nanopores for biomolecular confinement. They have been proposed as future templates for DNA encapsulation due to their hydrophobic nature ( Cruz et al, 2015 ).…”

“…Molecular Dynamics (MD) simulations of Cruz et al ( Cruz et al, 2014 ; Cruz et al, 2015 ) observed the spontaneous encapsulation of dsDNA in the 4 nm nanopore of a SWCNT, but not when the diameter narrowed down to 3 nm. They reported that this behavior is due to the confined dsDNA termini directly contacting the hydrophobic walls of the SWCNT with no solvent slab in-between.…”

“…Such high temperatures are physiologically irrelevant. Cruz et al ( Cruz et al, 2014 ; Cruz et al, 2015 ) and Nandy et al (2012) found that the contact between a dsDNA segment and the hydrophobic wall of a SWCNT results in some rearrangement of the H-bonds between the nucleobases and some of the base pairs that come on the contact of the SWCNT wall are melted. Jonchhe et al (2020) found that a DNA hairpin, when enclosed inside a nanocage, severely loses its mechanical and thermodynamic stability.…”

Melting of DNA in confined geometry

“…The thermodynamical spontaneity of DNA encapsulation of carbon nanotube under different conditions is still a significant area of research. The threshold diameter of this tube is also a vital issue to investigate since below the threshold encapsulation is inhibited [24]. Many sensitive parameters are involved in DNA encapsulation techniques like the medium and topology of the carrier, thermodynamic parameters, etc.…”