Xianren Zhang

Cooperative Effect in Receptor-Mediated Endocytosis of Multiple Nanoparticles

The uptake of nanoparticles (NPs) by a cellular membrane is known to be NP size dependent, but the pathway and kinetics for the endocytosis of multiple NPs still remain ambiguous. With the aid of computer simulation techniques, we show that the internalization of multiple NPs is in fact a cooperative process. The cooperative effect, which in this work is interpreted as a result of membrane curvature mediated NP interaction, is found to depend on NP size, membrane tension, and NP concentration on the membranes. While small NPs generally cluster into a close packed aggregate on the membrane and internalize, as a whole, NPs with intermediate size tend to aggregate into a linear pearl-chain-like arrangement, and large NPs are apt to separate from each other and internalize independently. The cooperative wrapping process is also affected by the size difference between neighboring NPs. Depending on the size difference of neighboring NPs and inter-NP distance, four different internalization pathways, namely, synchronous internalization, asynchronous internalization, pinocytosis-like internalization, and independent internalization, are observed.

Molecular modeling of the relationship between nanoparticle shape anisotropy and endocytosis kinetics

In this work, an N-varied dissipative particle dynamics (DPD) simulation technique is applied to investigate detailed endocytosis kinetics for ligand-coated nanoparticles with different shapes, including sphere-, rod- and disk-shaped nanoparticles. Our results indicate that the rotation of nanoparticles, which is one of the most important mechanisms for endocytosis of shaped nanoparticle, regulates the competition between ligand-receptor binding and membrane deformation. Shape anisotropy of nanoparticles divides the whole internalization process into two stages: membrane invagination and nanoparticle wrapping. Due to the strong ligand-receptor binding energy, the membrane invagination stage is featured by the rotation of nanoparticles to maximize their contact area with the membrane. While the kinetics of the wrapping stage is mainly dominated by the part of nanoparticles with the largest local mean curvature, at which the membrane is most strongly bent. Therefore, nanoparticles with various shapes display different favorable orientations for the two stages, and one or two orientation rearrangement may be required during the endocytosis process. Our simulation results also demonstrate that the shape anisotropy of nanoparticles generates a heterogeneous membrane curvature distribution and might break the symmetry of the internalization pathway, and hence induce an asymmetric endocytosis.

Nanobubble stability induced by contact line pinning

The origin of surface nanobubbles stability is a controversial topic since nanobubbles were first observed. Here, we propose a mechanism that the three-phase contact line pinning, which results from the intrinsic nanoscale physical roughness or chemical heterogeneities of substrates, leads to stable surface nanobubbles. Using the constrained lattice density functional theory (LDFT) and kinetic LDFT, we prove thermodynamically and dynamically that the state with nanobubbles is in fact a thermodynamical metastable state. The mechanism consistent with the classical nucleation theory can interpret most of experimental characteristics for nanobubbles qualitatively, and predict relationships among the gas-side nanobubble contact angle, nanobubble size, and chemical potential.

Replacement mechanism of methane hydrate with carbon dioxide from microsecond molecular dynamics simulations

Replacement of CH4 in hydrate form with CO2 is a candidate for recovering CH4 gas from its hydrates and storing CO2. In this work, microsecond molecular dynamics simulations were performed to study the replacement mechanism of CH4 hydrate by CO2 molecules. The replacement process is found to be controlled cooperatively by the chemical potentials of guest molecules, “memory effect”, and mass transfer. The replacement pathway includes the melting of CH4 hydrate near the hydrate surface and the subsequent formation of an amorphous CO2 hydrate layer. A large number of hydrate residual rings left after the melting of CH4 hydrate facilitate the nucleation of CO2 hydrate and enhance the dynamic process, indicating the existence of so-called “memory effect”. In the dynamic aspect, the replacement process takes place near the surface of CH4 hydrate rather easily. However, as the replacement process proceeds, the formation of the amorphous layer of the CO2 hydrate provides a significant barrier to the mass transfer of the guest CH4 and CO2 molecules, which prevents the CH4 hydrate from further dissociation and slows down the replacement rate.

Microsecond Molecular Dynamics Simulations of the Kinetic Pathways of Gas Hydrate Formation from Solid Surfaces

In this paper, we report microsecond molecular dynamics simulations of the kinetic pathway of CO(2) hydrate formation triggered by hydroxylated silica surfaces. Our simulation results show that the nucleation of the CO(2) hydrate is a three-stage process. First, an icelike layer is formed closest to the substrates on the nanosecond scale. Then, on the submicrosecond timescale, a thin layer with intermediate structure is induced to compensate for the structure mismatch between the icelike layer and the final stable CO(2) hydrate. Finally, on the microsecond timescale, the nucleation of the first CO(2) hydrate motif layer is generated from the intermediate structure that acts as nucleation seeds. We also address the effects of the distance between two surfaces.

Molecular understanding of receptor-mediated membrane responses to ligand-coated nanoparticles

The cytotoxicity of nanoparticles (NPs) and their potential applications in drug delivery and intracellular imaging have been extensively investigated, and a thorough molecular understanding of how cellular membrane responds to the introduction of NPs is essential for biomaterial design. In this work, N-varied dissipative particle dynamics (DPD) simulation is applied to investigate how a membrane responds to adsorption of ligand-coated NP. Depending on the membrane surface tension, ligand area density and NP size, four kinds of membrane responses are observed: membrane rupture, NP adhesion, NP penetration, and receptor-mediated endocytosis. While endocytosis provides an effective pathway for cellular uptake of NPs, the NP penetration and NP-induced membrane rupture are related to cytotoxicity. These results support the recent experimental reports that NPs have a Janus face for their biomedical applications: serving as carriers for the transmembrane transport of drug and causing cytotoxicity.

The relationship between membrane curvature generation and clustering of anchored proteins: a computer simulation study

The mechanism of biomembrane curvature generation has been studied for decades because of its role in many cellular functions. In this article, N-varied dissipative particle dynamics was used to investigate the relationship between membrane curvature generation and self-assembly of anchored proteins, and a protein aggregation mechanism of curvature generation was proposed. According to the mechanism, the curvature production is enhanced by the self-assembly of proteins, and the enhancement depends on the protein hydrophobic length. Contrary to the theoretic predictions that shallow insertion depth of proteins is more effective in producing positive membrane curvature, our simulations show the opposite trend if the self-assembly of proteins is taken into account. Furthermore, for the membrane proteins with deep insertion, simulations indicate that the self-assembly of proteins may induce membrane vesiculation at negative membrane tensions. In addition, the protein aggregates can sense the membrane curvature, although the way they respond to the local curvature again depends on the protein hydrophobic length. Especially, the self-assembly of shallow inserting proteins is significantly affected by the local membrane curvature.

A unified mechanism for the stability of surface nanobubbles: contact line pinning and supersaturation.

In this paper, we apply the molecular dynamics simulation method to study the stability of surface nanobubbles in both pure fluids and gas-liquid mixtures. First, we demonstrate with molecular simulations, for the first time, that surface nanobubbles can be stabilized in superheated or gas supersaturated liquid by the contact line pinning caused by the surface heterogeneity. Then, a unified mechanism for nanobubble stability is put forward here that stabilizing nanobubbles require both the contact line pinning and supersaturation. In the mechanism, the supersaturation refers to superheating for pure fluids and gas supersaturation or superheating for the gas-liquid mixtures, both of which exert the same effect on nanobubble stability. As the level of supersaturation increases, we found a Wenzel or Cassie wetting state for undersaturated and saturated fluids, stable nanobubbles at moderate supersaturation with decreasing curvature radius and contact angle, and finally the liquid-to-vapor phase transition at high supersaturation.

Capillary liquid bridges in atomic force microscopy: Formation, rupture, and hysteresis

Atomic force microscopy (AFM) can work in a variety of environment with different humidities. When the tip of AFM approaches a sample, the measured adhesion force would be significantly affected by the presence of nanometer-sized liquid bridge. The formation and rupture of liquid bridges can occur either through equilibrium or nonequilibrium process. In this work, the liquid bridges are assumed to be in thermodynamic equilibrium with the surrounding vapor medium. To study theoretically the stability of liquid bridge, a constraint is added into the lattice density functional theory to stabilize a series of bridges with different radii at a given tip-substrate distance. With the help of the constraint, we can identify not only stable and metastable states but also transition states for the formation and rupture of liquid bridges. Using this constrained method we calculate the energy barriers involved in the formation and rupture of the liquid bridges, respectively, and then discuss their stability as well as the origin of the hysteresis behavior observed with atomic force microscope measurements. On the whole, the calculated force-distance curves are found to be qualitatively in agreement with experimental observations. The energy barriers for the formation and rupture of liquid bridges are also analyzed as a function of tip-sample distance, humidity, and tip-fluid interaction.

A hybrid absorption–adsorption method to efficiently capture carbon

Removal of carbon dioxide is an essential step in many energy-related processes. Here we report a novel slurry concept that combines specific advantages of metal-organic frameworks, ion liquids, amines and membranes by suspending zeolitic imidazolate framework-8 in glycol-2-methylimidazole solution. We show that this approach may give a more efficient technology to capture carbon dioxide compared to conventional technologies. The carbon dioxide sorption capacity of our slurry reaches 1.25 mol l−1 at 1 bar and the selectivity of carbon dioxide/hydrogen, carbon dioxide/nitrogen and carbon dioxide/methane achieves 951, 394 and 144, respectively. We demonstrate that the slurry can efficiently remove carbon dioxide from gas mixtures at normal pressure/temperature through breakthrough experiments. Most importantly, the sorption enthalpy is only −29 kJ mol−1, indicating that significantly less energy is required for sorbent regeneration. In addition, from a technological point of view, unlike solid adsorbents slurries can flow and be pumped. This allows us to use a continuous separation process with heat integration.