Simulation of Nanoparticle Permeation through a Lipid Membrane

Abstract

A metric of nanoparticle toxicity is the passive permeability rate through cellular membranes. To assess the influence of nanoparticle morphology on this process, the permeability of buckyball-sized molecules through a representative lipid bilayer was investigated by molecular-dynamics simulation. When C(60) was compared with a prototypical opened C(60) molecule and a representative combustion-generated particle, C(68)H(29), the calculated free-energy profiles along the permeation coordinate revealed a sizable variation in form and depth. The orientation of the anisotropic molecules was determined by monitoring the principal axis corresponding to the largest moment of inertia, and free rotation was shown to be hindered in the bilayer interior. Diffusion constant values of the permeant molecules were calculated from a statistical average of seven to 10 trajectories at five locations along the permeation coordinate. A relatively minor variation of the values was observed in the bilayer interior; however, local resistance values spanned up to 24 orders of magnitude from the water layer to the bilayer center, due primarily to its exponential dependence on free energy. The permeability coefficient values calculated for the three similarly sized but structurally distinct nanoparticles showed a significant variance. The use of C(60) to represent similarly sized carbonaceous nanoparticles for assessments of toxicity is questioned.

Effect of Size and Surface Charge of Gold Nanoparticles on their Skin Permeability: A Molecular Dynamics Study

“…2a). Fiedler et al 48. reported similar small barrier near the interface of DPPC bilayer with hydrophobic carbon nanoparticle.…”

“…The magnitudes of the free energy minimum were lesser than similar sized neutral hydrophobic AuNP in this study. Fiedler et al 48. carried out constrained MD simulation of permeation of C60 (~1.25 nm) through DPPC bilayer and a very small barrier existed near the headgroup for permeation of hydrophobic C60 nanoparticle.…”

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

“…14 Recent molecular dynamics studies have focused on a wide variety of molecules passively diffusing through membranes, such as water, [15][16][17] small molecules, [18][19][20][21][22][23] model drug compounds, 6,22,24,25 analgesics, [26][27][28] drug delivery systems, 29,30 dyes, 31,32 other lipids, 33,34 nanoparticles, [35][36][37] toxins, 38 small peptides, 39,40 and even transmembrane proteins. 41,42 However, only a handful of MD studies have examined amino acid-related systems and are confined to tryptophan, [43][44][45] arginine, 46,47 lysine, 47 and amino acid analogues.…”

Chemical Basis of Interactions Between Engineered Nanoparticles and Biological Systems

“…The interactions of carbon nanoparticles, polymers and nanocrystals with lipid bilayers have been simulated by all-atom and coarse-grained approaches. 87-94 The influences of nanoparticle size, surface chemistry, hydrophobicity, shape and bilayer properties on the interaction mechanisms have been studied, and the results have yielded explanations for some experimental outcomes. 87,88,90,93,95-98 ENREF 70 …”