Molecular Understanding of the Penetration of Functionalized Gold Nanoparticles into Asymmetric Membranes

Abstract

In this work, the interactions between surface-functionalized gold nanoparticles (AuNPs) and asymmetric membranes and the associated cytotoxicity were explored by coarse-grained molecular dynamics simulations. Simulation results show that the surface chemistry of AuNPs and the asymmetry of lipid membranes play significant roles. AuNPs with different signs of charges spontaneously adhere to the membrane surface or penetrate the membrane core. Also, the asymmetric distribution of charged lipids in membranes can facilitate the penetration of cationic AuNPs. Increasing the surface charge density (SCD) of AuNPs can not only improve the penetration efficiency but also lead to more disruption of the membrane structure. Moreover, the flip-flop of charged lipids in the inner leaflet can be observed during the translocation of AuNPs with a high SCD. The breakdown of membrane asymmetry may hinder the cellular internalization of AuNPs in a direct penetration mechanism. More importantly, we demonstrate that the hydrophobic contact between protruding solvent-exposed lipid tails and the hydrophobic moieties of ligands can mediate the insertion of AuNPs with a low SCD into cell membranes, which will exhibit less cytotoxicity in most in vivo applications. This may open a new exciting avenue to developing nanocarriers with a higher translocation efficiency and a lower toxicity simultaneously for biomedical applications.

Toxicity of Nanomaterials: Exposure, Pathways, Assessment, and Recent Advances

“…The authors believed that the cationic Au NPs diffused directly inside the cells by disrupting the cell membrane . This postulation was further verified in several other publications. , Interaction of surface functionalized NPs leads to the damage of the integrity of cell membrane and results in pore generation. Other than the surface charge, the ligand interaction (after surface functionalization) also costs in variation in toxicity assessment. , Peetla et al studied the effect of the molecular structure of cationic ligand on the cellular uptake through a model membrane.…”

Structural behavior of amphiphilic polyion complexes interacting with saturated lipid membranes investigated by coarse-grained molecular dynamic simulations

“…60 It was also claimed that the charged ligand transfer across the membrane core and the subsequent membrane-spanning conguration was a rare event difficult to sample with coarse-grained simulations, and which was more appropriately evidenced using biasing simulation techniques 25,42 or asymmetric charged membranes. 40 More insights into the conformational changes undergone upon complex binding and intercalation in the bilayer inner region can be gained from the radius of gyration of the complex projected perpendicular and parallel to the bilayer surface R gxy,c R gz,c (Fig. 7).…”

“…An increased hydrophobic moiety decreased the lateral pressure required for the bilayer rupture and rendered the membrane more susceptible to mechanical stress. 36 According to atomistic and coarse-grained molecular dynamics simulations of the inorganic particles protected via amphiphilic ligands, 25,[37][38][39][40][41][42][43] these complexes could stably adhere to zwitterionic lipid bilayers and attained eventually the socalled "snorkeling" conformation, characterized by the nanoparticles embedded in the hydrophobic bilayer core and the charged ligands anchored to the charged moiety of both bilayer leaets. The complex bound initially to the bilayer via electrostatics, and the transition from this state to the snorkeling conguration proceeded through several distinct metastable congurations.…”

Multiscale Modeling and Simulation of Nano‐Carriers Delivery through Biological Barriers—A Review

“…This external potential could affect the interaction between the NPs and the membrane, especially the interaction between charged NPs and the polar membrane. For example, it has been shown that the change of the charge densities on the NPs may induce internalization of nanoparticles into cells through different pathways, such as passive translocation for nanoparticles with low charge density, or endocytosis for high charge density ( Figure a) …”