Computer simulation of the structural properties of fatty-acid modified PAMAM dendrimers at pH 5 and 7.

In this work, we performed coarse-grained molecular dynamics (CGMD) simulations of G3, G4, and G5 polyamidoamine (PAMAM) dendrimers grafting with fatty acid (FTA) chains. The FTA chains of varying length and grafting densities (50% and 100% of surface terminals) correspond to pH 7 and 5, respectively. Our findings suggested that the structural properties of dendrimers were determined by dendrimer generation, polymerization degrees, and pH. With one exception, the size of the FTA grafting dendrimer shrank after fatty acid attachment. Because of the protonation of the dendrimer's interior amines at low pH, the FTA chains are distributed at the dendrimer's surface group. At pH 7, the FTA chains that have aggregated in the interior of the dendrimer cause chain crowding. Our research provided references on drug encapsulation and the lower toxicity of these hydrophobically modified nanoparticles.

Unfolding of a diblock chain and its anomalous diffusion induced by active particles.

We study the structural and dynamical behavior of an A-B diblock chain in the bath of active Brownian particles (ABPs) by Brownian dynamics simulations in two dimensions. We are interested in the situation that the effective interaction between the A segments is attractive, while that between the B segments is repulsive. Therefore, in thermal (nonactive) equilibrium, the A block "folds" into a compact globule, while the B block is in the expanded coil state. Interestingly, we find that the A block could "unfold" sequentially like unknitting a sweater, driven by the surrounding ABPs when the propelling strength on them is beyond a certain value. This threshold value decreases and then levels off as the length of the B block increases. We also find a simple power-law relation between the unfolding time of the A block and the self-propelling strength and an exponential relation between the unfolding time and the length of the B block. Finally, we probe the translational and rotational diffusion of the chain and find that both of them show "super-diffusivity" in a large time window, especially when the self-propelling strength is small and the A block is in the folded state. Such super-diffusivity is due to the strong asymmetric distribution of ABPs around the chain. Our work provides new insights into the behavior of a polymer chain in the environment of active objects.

Molecular dynamics simulation of G-actin interacting with PAMAM dendrimers.

Understanding the interactions of dendrimers as drug/gene delivery vectors with proteins is important for functional optimization. Here, atomistic molecular dynamics simulations are employed to study the interactions between six positively-charged polyamidoamine dendrimers of the second generation (G2 PAMAM) and G-actin. We find that the structure of G-actin is relatively stable after dendrimers' binding. PAMAM dendrimers also do not significantly change the secondary structure of G-actin. Furthermore, we find the formation of dendrimer-actin complex is mainly driven by electrostatic interactions. Moreover, we suggest the secondary structure change of local domains of G-actin is probably responsible to the inhibition of actin polymerization.

Beating of grafted chains induced by active Brownian particles.

We study the interplay between active Brownian particles (ABPs) and a "hairy" surface in two-dimensional geometry. We find that the increase of propelling force leads to and enhances inhomogeneous accumulation of ABPs inside the brush region. Oscillation of chain bundles (beating like cilia) is found in company with the formation and disassembly of a dynamic cluster of ABPs at large propelling forces. Meanwhile chains are stretched and pushed down due to the effective shear force by ABPs. The decrease of the average brush thickness with propelling force reflects the growth of the beating amplitude of chain bundles. Furthermore, the beating phenomenon is investigated in a simple single-chain system. We find that the chain swings regularly with a major oscillatory period, which increases with chain length and decreases with the increase of propelling force. We build a theory to describe the phenomenon and the predictions on the relationship between the period and amplitude for various chain lengths, and propelling forces agree very well with simulation data.

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.