Endohedral confinement of a DNA dodecamer onto pristine carbon nanotubes and the stability of the canonical B form

TL;DR

This study demonstrates that sufficiently large carbon nanotubes can thermodynamically favorably encapsulate DNA segments under physiological conditions, maintaining their structure and mobility, which is promising for drug delivery applications.

Contribution

First demonstration of thermodynamic favorability of DNA encapsulation in large carbon nanotubes under physiological conditions using enhanced sampling techniques.

Findings

Encapsulation is favorable in nanotubes with diameter ≥3 nm.

Confined DNA maintains its B-form structure and mobility.

End-to-end length of DNA increases slightly during encapsulation.

Abstract

Although carbon nanotubes are potential candidates for DNA encapsulation and subsequent delivery of biological payloads to living cells, the thermodynamical spontaneity of DNA encapsulation under physiological conditions is still a matter of debate. Using enhanced sampling techniques, we show for the first time that, given a sufficiently large carbon nanotube, the confinement of a double-stranded DNA segment, 5'-D(*CP*GP*CP*GP*AP*AP*TP*TP*CP*GP*CP*G)-3', is thermodynamically favourable under physiological environments (134 mM, 310 K, 1 bar), leading to DNA-nanotube hybrids with lower free energy than the unconfined biomolecule. A diameter threshold of 3 nm is established below which encapsulation is inhibited. The confined DNA segment maintains its translational mobility and exhibits the main geometrical features of the canonical B form. To accommodate itself within the nanopore, the DNA end-to-end length increases from 3.85 nm up to approximately 4.1 nm, due to a 0.3 nm elastic expansion of the strand termini. The canonical Watson-Crick H-bond network is essentially conserved throughout encapsulation, showing that the contact between the DNA segment and the hydrophobic carbon walls results in minor rearrangements of the nucleotides H-bonding. The results obtained here are paramount to the usage of carbon nanotubes as encapsulation media for next generation drug delivery technologies.