Nanoparticle penetration into cell membranes is an interesting phenomenon that may have crucial implications on the nanoparticles' biomedical applications. In this paper, a coarse-grained model for gold nanoparticles (AuNPs) is developed (verified against experimental data available) to simulate their interactions with model lipid membranes. Simulations reveal that AuNPs with different signs and densities of surface charges spontaneously adhere to the bilayer surface or penetrate into the bilayer interior. The potential of mean force calculations show that the energy gains upon adhesion or penetration is significant. In the case of penetration, it is found that defective areas are induced across the entire surface of the upper leaflet of the bilayer and a hydrophilic pore that transports water molecules was formed with its surrounding lipids highly disordered. Penetration and its concomitant membrane disruptions can be a possible mechanism of the two observed phenomena in experiments: AuNPs bypass endocytosis during their internalization into cells and cytotoxicity of AuNPs. It is also found that both the level of penetration and membrane disruption increase as the charge density of the AuNP increases, but in different manners. The findings suggest a way of controlling the AuNP-cell interactions by manipulating surface charge densities of AuNPs to achieve designated goals in their biomedical applications, such as striking a balance between their cellular uptake and cytotoxicity in order to achieve optimal delivery efficiency as delivery agents.

The mutual effects of two crucial features of carbon nanotubes (CNTs) (surface and confinement) on the temperature-dependent water diffusion are studied through molecular dynamics simulations. A two-stage diffusion mechanism is detected in the CNTs of diameter smaller than 12.2 Å, which becomes obscure as the temperature increases. This peculiar phenomenon can be ascribed to the cooperation of the small confinement and the periodic surface. The diffusion coefficient of the confined water exhibits a nonmonotonic dependence on the confinement size and an unexpected increase inside the large CNTs (compared to that of bulk water). These anomalous behaviors can be attributed to the competition of the smooth surface and the small confinement. Considering the mutual effects, an empirical formula is proposed on the basis of two groups of numerical examples, whose results indicate that the confinement effect will dominate over the surface effect until the CNT diameter increases up to ~16 Å, whereas thereafter the surface effect becomes dominant and finally both of them vanish gradually.

The diffusion mechanism and coefficient of water confined in carbon nanotubes (CNTs) of diameter ranging from 8 to 54 Å are studied by molecular dynamics simulations. It is found that the motions of water molecules inside the CNTs of diameter smaller than 12.2 Å follow a two-stage diffusion mechanism. Initially, the water diffusion exhibits a long-time super-or sub-diffusion mechanism, and thereafter it transits to the single-file type inside the (6, 6) CNT and shifts to the Fickian type inside the larger CNTs. As for the CNTs of diameter larger than 12.2 Å , the diffusion of the confined water occurs through the Fickian mechanism, which is identical to that of the bulk water. The simulation results further reveal that the diffusion coefficient of the confined water is non-monotonically dependent on the diameter, which can be ascribed to the double-edged effect of CNTs, i.e., the surface effect and the size effect.

Understanding the interactions of gold nanoparticles (AuNPs) with cellular compartments, especially cell membranes, is of fundamental importance in obtaining their control in biomedical applications. An effort is made in this paper to investigate the interactions of 2.2 nm core AuNPs with negative model bilayer membranes by coarse-grained (CG) molecular dynamics (MD) simulation. The CG model of lipid bilayer was taken from Marrink et al. ( J. Phys. Chem. B 2004, 108, 750-760 ), whereas the CG AuNPs model was developed on the basis of both atomistic MD simulations and experimental data. It was found that AuNPs functionalized with cationic ligands penetrated into the negative bilayer membranes and generated significant disruptions on bilayers. The lipids surrounding the nanoparticle were highly disordered and the bulk surface of the bilayer exhibits some defective areas. Most importantly, it is observed that a nanoscale hole can be formed and expanded spontaneously on the peripheral regions of the 20 × 20 nm bilayer. The expansion of the hole is on the time scale of hundreds of nanosceonds. The fully expanded hole had a radius of ∼5.5 nm and could transport water molecules at a rate of up to ∼1100 molecule/ns. However holes could not be formed on a larger bilayer (28 × 28 nm). The factors that can eliminate hole formation on the bilayer also include the decrease of cationic lignads on the AuNP, the reduction of negative lipids in the bilayer, the release of bilayer surface tension, the lowering of temperature, and the addition of a high concentration of salt. The results suggest that a hole can only be formed on living cell membranes under extreme conditions.

The influences of the diameter (size) of single-walled carbon nanotubes (SWCNTs) and the temperature on the viscosity of water confined in SWCNTs are investigated by an "Eyring-MD" (molecular dynamics) method. The results suggest that the relative viscosity of the confined water increases with increasing diameter and temperature, whereas the size-dependent trend of the relative viscosity is almost independent of the temperature. Based on the computational results, a fitting formula is proposed to calculate the size- and temperature- dependent water viscosity, which is useful for the computation on the nanoflow. To demonstrate the rationality of the calculated relative viscosity, the relative amount of the hydrogen bonds of water confined in SWCNTs is also computed. The results of the relative amount of the hydrogen bonds exhibit similar profiles with the curves of the relative viscosity. The present results should be instructive for understanding the coupling effect of the size and the temperature at the nanoscale.

Coarse-grained (CG) molecular dynamics (MD) simulations were carried out to investigate the dynamics of 2.2 nm monolayer-protected gold nanoparticles (AuNPs) in solvents. The effects of ligand length, ligand terminal chemistry, solvents, and temperature were examined. It was found that AuNPs with unmodified alkanethiol ligands formed stable aggregates in water in the time scale of hundreds of nanoseconds (eight nanoparticles). In a particular case, the AuNPs aggregated into an infinite, one-dimensional chainlike assembly instead of clusters of aggregates. The aggregates of AuNPs with short ligand tails seemed to have an amorphous shape, whereas long-tailed AuNPs aggregated into a spherical cluster. The properties of ligand terminals had a dominant influence on the aggregation behavior of AuNPs. Increasing the polarity of the ligand terminals weakened the tendency of aggregation of AuNPs in water. For AuNPs imposed with charged terminals, they did not aggregate even with a high concentration of salt. However the aggregation behavior of AuNPs changed dramatically if the properties of solvent were altered. Temperature increase greatly accelerated the process of aggregation. The results suggest that the dynamics of monolayer-protected AuNPs can be controlled by their surface properties as well as the features of solvents.

In this paper, the viscosity of water confined in single-walled carbon nanotubes (SWCNTs) with the diameter ranging from 8 to 54 Å is evaluated, which is crucial for the research on the nanoflow but difficult to be obtained. An ''Eyring-MD'' (molecular dynamics) method combining the Eyring theory of viscosity with the MD simulations is proposed to tackle the particular problems. For the critical energy which is a parameter in the ''Eyring-MD'' method, the numerical experiment is adopted to explore its dependence on the temperature and the potential energy. To demonstrate the feasibility of the proposed method, the viscosity of water at high pressure is computed and the results are in reasonable agreement with the experimental results. The computational results indicate that the viscosity of water inside SWCNTs increases nonlinearly with enlarging diameter of SWCNTs, which can reflect the size effect on the transports capability of the SWCNTs. The trend of the viscosity is well explained by the variation of the hydrogen bond of the water inside SWCNTs. A fitting equation of the viscosity of the confined water is given, which should be significant for recognizing and studying the transport behavior of fluid through the nanochannels.

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