Jia-Wei Shen

Induced stepwise conformational change of human serum albumin on carbon nanotube surfaces

Non-covalent adsorption of proteins onto carbon nanotubes is important to understand the environmental and biological activity of carbon nanotubes as well as their potential applications in nanostructure fabrication. In this study, the adsorption dynamics and features of a model protein (the A sub-domain of human serum albumin) onto the surfaces of carbon nanotubes with different diameters were investigated out by molecular dynamics simulation. The adsorption behaviors were observed by both trajectory and quantitative analyses. During the adsorption process, the secondary structures of alpha-helices in the model protein were slightly affected. However, the random coils connecting these alpha-helices were strongly affected and this made the tertiary structure of protein change. The conformation and orientation selection of the protein were induced by the properties and the texture of surfaces indicated by the interaction curve. In addition, the stepwise adsorption dynamics of these processes are found. The mechanism of induced stepwise conformational change of protein on carbon nanotube surfaces would be helpful to better understand the protein-surface interaction at the molecular level.

On the spontaneous encapsulation of proteins in carbon nanotubes

Biomolecules-carbon nanotube (CNT) interactions are of great importance in CNT-based drug delivery systems and biomedical devices. In this study, a spontaneous encapsulation of a globular protein into the CNT was observed through molecular dynamics simulation. The free energy of the system was found to be decreased after the encapsulation, which is the most fundamental reason for this spontaneous process. The system enthalpy decrease was found to make a dominant contribution to the free-energy change, and the system entropy increase also contributes to the spontaneous process. During the insertion, the protein makes a stepwise conformational change to maximize its affinity to the CNT walls as well as the protein-CNT interactions, mainly resulting in the deformation of the beta-sheets in the protein. As a whole, the CNT was considered to attract protein molecules nonspecifically although the groups with high hydrophobicity and/or aromatic rings show great affinity.

Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model

Therapeutic strategies based on modulation of microRNA activity possess much promise in cancer therapy, but the in vivo delivery of microRNA to target sites and its penetration into tumor tissues remain great challenge. In this work, miR-34a-delivering therapeutic nanocomplexes with a tumor-targeting and -penetrating bifunctional CC9 peptide were proposed for efficient treatment of pancreatic cancers. In vitro study indicated that the nanoparticle-based miR-34a delivery systems could effectively facilitate cellular uptake and greatly up-regulate the mRNA level of miR-34a in PANC-1 cell lines. The up-regulation of miR-34a remarkably induced cell cycle arrest and apoptosis, suppressed the tumor cell migration and inhibited the target gene expressions such as E2F3, Bcl-2, c-myc and cyclin D1. More importantly, the in vivo systemic administration of the developed targeting miR-34a delivery systems in a pancreatic cancer model significantly inhibited tumor growth and induced cancer cell apoptosis. Such bifunctional peptide-conjugated miRNA-delivering nanocomplexes should have great potential applications in cancer therapy.

Shield effect of silicate on adsorption of proteins onto silicon-doped hydroxyapatite (100) surface

Protein adsorption-desorption on nanoscale surface plays a key role in biomaterials, cell adhesion, biosensors, biofuel cells and biomineralization. Silicate-substituted hydroxyapatite (SiHA) is one of the most interesting bioceramics in the field of bioactive hard tissue implants. In this paper, the adsorption-desorption behaviors of leucine-rich amelogenin protein (LRAP) on a series of SiHA (100) surfaces were investigated using the molecular dynamics (MD), steered molecular dynamics (SMD) simulations and density functional theory (DFT) calculations. It was found that the silicate ions on SiHA (100) surface cause a shield effect, which was composed of the charge repulsion and the steric hindrance of silicates. These findings suggest that surface engineering technologies can be potentially used to directly control/manufacture the nanoscale surface texture and the composition of material surfaces, thereby to mediate the interaction of proteins with biomaterials.

A gene nanocomplex conjugated with monoclonal antibodies for targeted therapy of hepatocellular carcinoma.

To enhance tumor-targeting abilities and therapeutic efficiency, a monoclonal antibody-conjugated gene nanocomplex was herein designed. The biodegradable cationic polyethylenimine-grafted-α,β-poly(N-3-hydroxypropyl)-DL-aspartamide (PHPA-PEI) was used for complexing pDNA to form the PHPA-PEI/pDNA nanoparticle, and then 9B9 mAb, an anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody, was conjugated to produce the PHPA-PEI/pDNA/9B9 mAb (PP9mN) complex. The PP9mN complex with the diameter of around 300 nm at its optimal weight ratio could be uptaken effectively by SMMC-7721 cells. The cytotoxicity of the PP9mN complex was much lower than that of PEI 25 kD in SMMC-7721, HepG2, Bel-7404 and COS-7 cell lines. The PP9mN complex possessed the highly efficient in vitro gene delivery ability to the hepatocellular carcinoma cells. The in vivo gene expression indicated that PP9mN could target to the tumor tissues effectively. By using the therapeutic AChE gene, it was found that the PP9mN complexes significantly enhanced the anti-tumor effect on tumor-bearing nude mice. Such monoclonal antibody-conjugated gene complex should have great potential applications in liver cancer therapy.

Diameter Selectivity of Protein Encapsulation in Carbon Nanotubes

Biomolecular-carbon nanotube (CNT) complexes are of great importance in biological and biomedical devices, and recently spontaneous encapsulation of biomolecules into CNTs has attracted great interest. In this work, we explored the diameter selectivity of the protein encapsulation in CNTs via molecular dynamics simulations, and the free energy changes of the systems were calculated for mechanism exploration. It is proved that there is an optimal tube size which provides the most effective encapsulation for a given protein molecule, and the encapsulations in the overlarge and overcrowded tubes are hindered by different factors based on the analysis of system energy contribution. In addition, the significance of the solvents for the system is also of concern.

Adsorption of Insulin Peptide on Charged Single‐Walled Carbon Nanotubes: Significant Role of Ordered Water Molecules

Ordered hydration shells: The more ordered hydration shells outside the charged CNT surfaces prevent more compact adsorption of the peptide in the charged CNT systems [picture: see text], but peptide binding strengths on the charged CNT surfaces are stronger due to the electrostatic interaction.Studies of adsorption dynamics and stability for peptides/proteins on single-walled carbon nanotubes (SWNTs) are of great importance for a better understanding of the properties and nature of nanotube-based biosystems. Herein, the dynamics and mechanism of the adsorption of the insulin chain B peptide on different charged SWNTs are investigated by explicit solvent molecular dynamics simulations. The results show that all types of surfaces effectively attract the model peptide. Water molecules play a significant role in peptide adsorption on the surfaces of charged carbon nanotubes (CNTs). Compared to peptide adsorption on neutral CNT surfaces, the more ordered hydration shells outside the tube prevent more compact adsorption of the peptide in charged CNT systems. This shield effect leads to a smaller conformational change and van der Waals interaction between the peptide and surfaces, but peptide binding strengths on charged CNT surfaces are stronger than those on the neutral CNT surface due to the strong electrostatic interaction. The result of these simulations implies the possibility of improving the binding strength of peptides/proteins on CNT surfaces, as well as keeping the integrity of the peptide/protein conformation in peptide/protein-CNT complexes by charging the CNTs.

Molecular Dynamics Simulation on Stability of Insulin on Graphene

The adsorption dynamics of a model protein (the human insulin) onto graphene surfaces with different sizes was investigated by molecular dynamics simulations. During the adsorption, it has different effect on the stability of the model protein in the fixed and non-fixed graphene systems. The tertiary structure of the protein was destroyed or partially destroyed, and graphene surfaces shows the selective protection for some -helices in non-fixed systems but not in fixed systems by reason of the flexibility of graphene. As indicated by the interaction energy curve and trajectory animation, the conformation and orientation selection of the protein were induced by the properties and the texture of graphene surfaces. The knowledge of protein adsorption on graphene surfaces would be helpful to better understand stability of protein on graphene surfaces and facilitate potential applications of graphene in biotechnology.

Conformational Mobility of GOx Coenzyme Complex on Single- Wall Carbon Nanotubes

A critical issue in bioelectrochemical applications that use electrodes modified by Single Wall Carbon Nanotubes (SWCNTs) is to ensure high activity of the catalytic site of an immobilized enzyme protein interacting with nanomaterials. Since Flavin Adenine Dinucleotide (FAD), a coenzyme of glucose oxidase (GOx), is the active center of the catalytic site, conformation of which could determine the activity of enzyme, it is important to understand the dynamic mechanism of its conformational mobility while GOx is adsorbed on SWCNTs with multiple orientations. However, this dynamic mechanism still remains unclear at the atomic level due to the coenzyme being embedded in the apo-GOx and the limitations of appropriate experimental methods. In this study, a molecular dynamics (MD) simulation was performed to investigate the conformational mobility mechanism of the coenzyme. The trajectory and the interaction energy clearly indicate that the adsorption of GOx onto SWCNTs plays an important role in the conformational mobility of the coenzyme, and its mobility is greatly affected by the distribution of water molecules due to it being hydrophobic.

Quantum mechanics study on the selectivity of alkali metal cations by a novel fluorescent chemosensor

The selectivity of alkali metal cations (Na+ and K+) by a novel fluorescent chemosensor was investigated by quantum mechanics calculations. The binding energy calculations of the cationic complexes indicate that both of the aza-18-crown-6 rings bind Na+ more strongly than K+ and ring A favors both of Na+ and K+ comparing to ring B. The order of the stability implied by Gibbs free energy study agrees with that by binding energy calculation. Solvent effect was further investigated. Due to the large difference of solvation energies, the order of the stability of complexes changes in water.