Adsorption of the Full Length Amyloid Beta Peptide on the Carbon Nanotube Surface and the Thermodynamic Implications for Fibrillogenesis

Abstract

Nanomaterials such as carbon nanotubes have gained recent attention, in part due to their potential applicability in biology and medicine. However, there are relatively few studies at the single-molecule level that explore the interactions of nanomaterials with biological building blocks such as peptides and proteins. Using fully atomistic molecular dynamics (MD) simulations at physiological temperatures, we have investigated the mechanism of adsorption of the full length, 42-residue, monomeric Amyloid beta peptide on the surface of a single walled carbon nanotube (SWCNT) of small diameter. Starting with different relative orientations of the peptide and the SWCNT that delineate the interactions arising from different important segments of the peptide, we find rapid convergence in the peptide's adsorption behavior within tens of nanoseconds, manifested in the arrested movement of the peptide in the nanotube's vicinity, in the convergence between the peptide-nanotube contact areas and approach distances, and in the observed increase of peptide curvature around the nanotube. Probing the interactions of different residue segments with the SWCNT, we find that the peptide's adsorption is initiated by interactions arising from the central hydrophobic core, and precipitated by the residues belonging to the N-terminal region. Adaptive biasing force based potential of mean force (PMF) calculations estimating the free energy changes as the peptide strands collapse towards each other demonstrate that the SWCNT causes the ‘open’ and the ‘collapsed’ states to be in near equilibrium, by bringing down the energetic cost of ‘loop opening’. The observed phenomena of peptide localization and decreased propensity for loop collapse could have important implications for site-directed drug delivery and for altering the kinetics of the peptide's self assembly.