In Silico Investigation on the Selective Nanotoxicity of Two-Dimensional Materials to Hen Egg White Lysozyme Protein

Abstract

Inspired by the urge to determine the underlying mechanism of the induction of toxic effects of state-of-the-art two-dimensional (2D) nanomaterials such as graphene and hexagonal boron nitride (h-BN) toward biomolecules, herein we study the interactions between these nanomaterials with a model protein hen egg white lysozyme (HEWL), employing classical molecular dynamics simulations. It is revealed that the protein gets easily adsorbed on both of the 2D materials, with the interaction energy being much higher in the case of h-BN, suggesting a significantly stronger adsorption affinity. The interactions of aromatic amino acid residues such as tyrosine and tryptophan along with few aliphatic residues such as arginine, lysine, and asparagine with the 2D materials are found to be pronounced, and most of the residues taking part in adsorption are nearly the same for both materials. While the secondary structure of HEWL remains nearly unaltered upon adsorption on graphene, h-BN massively perturbs both the α-helix and β-sheet components through the disruption of intraprotein hydrogen bonds, which are in turn sine quo non for the preservation of the structural integrity. It is demonstrated that the disruption of the secondary structure is due to pronounced thermodynamic preference for the adsorption of the constituent amino acid residues on h-BN compared to their spatial disposition within the proteins. The calculated release times from the adsorbed state are found to be orders of magnitude higher in the case of h-BN compared to graphene, and it is unlikely that the protein would get released in accessible time scales unless dislodged by the application of an external force. The present study contributes to the fundamental understanding of the nanotoxicity of emerging 2D materials toward proteins, thereby aiding experimentalists to design biocompatible 2D materials for nano-biomedical usage and device fabrication.