Effect of Nanoparticle Curvature on Its Interaction with Serum Proteins.

The size or the curvature of nanoparticles (NPs) plays an important role in regulating the composition of the protein corona. However, the molecular mechanisms of how curvature affects the interaction of NPs with serum proteins still remain elusive. In this study, we employ all-atom molecular dynamics simulations to investigate the interactions between two typical serum proteins and PEGylated Au NPs with three different surface curvatures (0, 0.1, and 0.5 nm-1, respectively). The results show that for proteins with a regular shape, the binding strength between the serum protein and Au NPs decreases with increasing curvature. For irregularly shaped proteins with noticeable grooves, the binding strength between the protein and Au NPs does not change obviously with increasing curvature in the cases of smaller curvature. However, as the curvature continues to increase, Au NPs may act as ligands firmly adsorbed in the protein grooves, significantly enhancing the binding strength. Overall, our findings suggest that the impact of NP curvature on protein adsorption may be nonmonotonic, which may provide useful guidelines for better design of functionalized NPs in biomedical applications.

Controlling the Interaction of Nanoparticles with Cell Membranes by the Polymeric Tether.

The well control over the cell-nanoparticle interaction can be of great importance and necessity for different biomedical applications. In this work, we propose a new and simple way (i.e., polymeric tether) to tuning the interaction between nanoparticles and cell membranes by dissipative particle dynamics simulations. It is found that the linked nanoparticles (via polymeric tether) can show some cooperation during the cellular uptake and thereby have a higher wrapping degree than the single nanoparticle. The effect of the property of the polymer on the wrapping is also investigated, and it is found that the length, rigidity, and hydrophobicity of the polymer play an important role. More interestingly, the uptake of linked nanoparticles could be adjusted to the firm adhesion via two rigid polymeric tethers. The present study may provide some useful guidelines for novel design of functional nanomaterials in the experiments.

Vesicle deposition and subsequent membrane-melittin interactions on different substrates: a QCM-D experiment.

Quartz crystal microbalance with dissipation (QCM-D) technique is one of the most effective methods to monitor the dynamic behaviors of a layer on a solid surface. Moreover, it has been reported recently that it is able to provide a fingerprint for the peptide-membrane interactions. In this work, QCM-D technique combined with computer simulations was employed to investigate the deposition and transformation of vesicles, as well as the subsequent membrane-melittin interactions on different substrates. A range of substrate surfaces, i.e. naked SiO2 without or with Au/polyelectrolyte coating, were produced. The nature of the substrate determined whether the adsorbed vesicles were present as a high-quality supported bilayer or an assembled vesicle matrix, which consequently influenced the membrane-melittin interactions. It was indicated by the related computer simulations that the lipid packing state of the membrane was a key factor to determine the mechanism of membrane-peptide interactions. Furthermore, this work might be a good example of the application of QCM-D for the exploration of membrane-active peptides.

Enhancing the targeting ability of nanoparticles via protected copolymers.

It is important to maintain the balance between therapeutic efficiency and cytotoxicity when using nanomaterials for biomedical applications. Here, we propose a new method (i.e., non-covalent coating of protected copolymers onto the nanoparticle surface) to enhance the active targeting of nanoparticles to the cancer cells by combining the dissipative particle dynamics simulation and in vitro experiments. When coating the protected copolymer onto the nanoparticle surface, the uptake efficiency could be greatly altered due to the competition between the copolymer-ligand interaction and the receptor-ligand interaction-the non-covalent coating is more efficient than the covalent coating. Furthermore, the effect of the physicochemical properties of the protected copolymer on the targeting ability of nanoparticles was also investigated. This study offers useful insight into the optimal design of nanocarriers in biomedicine.

Shape deformation and fission route of the lipid domain in a multicomponent vesicle.

In this paper, the curvature changes and fission routes of the lipid domains in a multicomponent vesicle are studied by dissipative particle dynamics. Under different conditions of asymmetric distribution of lipids in two leaflets of lipid bilayer and area-to-volume ratio of the vesicle, we obtained different configurations of the domain in the vesicle: three typical curvature characters of the lipid domain, namely, positive, negative, and invariable curvatures compared to the vesicle are observed. Furthermore, some other morphologies of the domain and two vesicle fission routes (i.e., exocytic and endocytic fissions) are also obtained in our simulations. Particular emphasis is put on the formation of the negative curvature domain and on the behavior of endocytic fission. Based on our simulations, it is indicated that water plays an important role in the invagination and endocytic fission processes of the domain in a vesicle. For endocytic fission, domains of different sizes are evolved according to different routes under the effect of the water. Additionally, we find that both the spontaneous curvature of lipid molecules and area-to-volume ratio can promote or restrain the shape deformation of the lipid domain. Under the competition of these two factors, another possible route of endocytic fission is observed in our simulations, in that only a part of the lipid domain invaginates into the interior of the vesicle to complete the endocytic fission. Our study is helpful for understanding the possible mechanism of the shape transformation of the cellular membrane and the difference of several kinds of routes of vesicle fission.

Designing a nanoparticle-containing polymeric substrate for detecting cancer cells by computer simulations.

Efficient and accurate detection of cancer cells (from normal cells) is of great importance in cancer diagnosis and prognosis. In this work, we design a new type of polymeric substrate containing nanoparticles for detecting cancers by the dissipative particle dynamics (DPD) simulation. It is found that the cancer cells and the normal cells can be indeed distinguished since the uptake number of nanoparticles from the substrate is different. The competition between the nanoparticle-cell specific interaction and nanoparticle-polymer non-specific interaction is the main factor for different uptake behaviors. Moreover, the dynamics of the nanoparticle diffusion in the polymer layer also plays an important role in the detection. To improve the detection accuracy, we further investigate the effect of the polymer type and density as well as the ligand type on the detection, and find that there may exist an optimal parameter to maximize the difference between cancer cells and normal cells. The present study may provide useful insights into the design of functionalized substrate-based nanodevices in biomedicine.

Polymer-Nucleic Acid Interactions.

Gene therapy is an important therapeutic strategy in the treatment of a wide range of genetic disorders. Polymers forming stable complexes with nucleic acids (NAs) are non-viral gene carriers. The self-assembly of polymers and nucleic acids is typically a complex process that involves many types of interaction at different scales. Electrostatic interaction, hydrophobic interaction, and hydrogen bonds are three important and prevalent interactions in the polymer/nucleic acid system. Electrostatic interactions and hydrogen bonds are the main driving forces for the condensation of nucleic acids, while hydrophobic interactions play a significant role in the cellular uptake and endosomal escape of polymer-nucleic acid complexes. To design high-efficiency polymer candidates for the DNA and siRNA delivery, it is necessary to have a detailed understanding of the interactions between them in solution. In this chapter, we survey the roles of the three important interactions between polymers and nucleic acids during the formation of polyplexes and summarize recent understandings of the linear polyelectrolyte-NA interactions and dendrimer-NA interactions. We also review recent progress optimizing the gene delivery system by tuning these interactions.

Designing new strategy for controlling DNA orientation in biosensors.

Orientation controllable DNA biosensors hold great application potentials in recognizing small molecules and detecting DNA hybridization. Though electric field is usually used to control the orientation of DNA molecules, it is also of great importance and significance to seek for other triggered methods to control the DNA orientation. Here, we design a new strategy for controlling DNA orientation in biosensors. The main idea is to copolymerize DNA molecules with responsive polymers that can show swelling/deswelling transitions due to the change of external stimuli, and then graft the copolymers onto an uncharged substrate. In order to highlight the responsive characteristic, we take thermo-responsive polymers as an example, and reveal multi-responsive behavior and the underlying molecular mechanism of the DNA orientation by combining dissipative particle dynamics simulation and molecular theory. Since swelling/deswelling transitions can be also realized by using other stimuli-responsive (like pH and light) polymers, the present strategy is universal, which can enrich the methods of controlling DNA orientation and may assist with the design of the next generation of biosensors.

Controlling cellular uptake of nanoparticles with pH-sensitive polymers.

The major challenge in cancer therapy is to efficiently translocate drug molecules into cancer tumors without doing any damage to healthy tissues. Since there exist pH gradients between tumor and normal tissues, pH-sensitive materials may have great potential to overcome such challenge. Here, we report one new type of pH-responsive drug delivery system where pH-sensitive polymers are introduced to control the cellular uptake of nanoparticles under different pH environments through dissipative particle dynamics simulations. Interestingly, the behavior of cellular uptake of nanoparticles here exhibits "smart" pH-responsive properties: for lower and higher pH, the nanoparticles can be taken up by cell membranes, while for pH in middle range, the endocytosis is blocked. Further, it is found that receptor-ligand interactions as well as surface charge property of nanoparticles and membranes can also have important impacts on the endocytosis. The present study may give some significant insights into future stimulus-responsive medical materials design.

Design maps for cellular uptake of gene nanovectors by computer simulation.

Understanding how nanovectors transport DNA molecules through cell membranes is of great importance in gene therapy. In this paper, we systematically investigate the mechanism of cellular uptake of cationic polymeric nanovectors containing DNA molecules through dissipative particle dynamics simulations. Our results show that the property of polyelectrolyte chains grafted to nanovector and DNA molecules can have important impacts on the endocytosis. Interestingly, it is found that the nanovector can be fully taken up with proper number of DNA molecules on its surface. On the contrary, in the absence of DNA it may become harder to be totally engulfed. Since the adsorption number of DNA is related to external pH, the cellular uptake could exhibit pH-responsive behavior. Further, we also provide insights into the comparison of uptake behaviors between cancer and normal cells, and importantly, we find that the enhanced uptake of gene nanovectors may be an inherent property of cancer cells. The present study may give some significant suggestions on future nanovector design for gene delivery.

Membrane-mediated interactions between nanoparticles on a substrate.

Investigations of the interactions between nanoparticles and lipid bilayer may yield insight into the understanding of the protein-biomembrane interactions and the cytotoxicity of drugs. Here, we theoretically investigate the membrane-mediated interactions between two nanoparticles supported on a substrate. We examine the effects of the packing density of lipids, the direct nanoparticle-lipid interaction, and the direct substrate-lipid interaction on the effective interactions between the nanoparticles and find the effective interactions between the two nanoparticles are mainly dominated by the competition of the deformations of the different parts of the lipid bilayers as well as the stretching of the lipid chains sandwiched between the nanoparticles. By varying the above-mentioned effects, the effective interactions between the two nanoparticles can be efficiently modulated. The results may provide some theoretical insight into experiments on the membrane-mediated nanoparticle organization on a substrate and organization of the membrane proteins or drug nanoparticles on the surfaces of the cellular membranes.