Effect of grafting density on the self-assembly of side-chain discotic liquid crystalline polymers with triphenylene discogens.

The self-assembly of triphenylene (TP)-based side-chain discotic liquid crystalline polymers (SDLCPs) with different grafting densities was investigated by using the dissipative particle dynamics (DPD) method. We explored the coupling effect between the main chain and the side-chain TP discogens with various length alkyl tails, and how the rigidity of the main chain, grafting density and spacer lengths affect the self-assembled morphologies of SDLCPs. By changing the above factors, we have obtained nine phases. It is deduced that a moderate grafting density, a polymer backbone with sufficient length and alkyl tails with medium length ensure SDLCPs form ordered columnar mesophases. It is worth noting that double columnar phases (Colne-Col and Colh-Col) were obtained with high grafting densities and sufficiently long backbones. All these results provide an effective basis and helpful guidance for the in-depth research of such kinds of fascinating organic semiconducting materials, SDLCPs, from the perspective of grafting density.

Simulating Surface Patterning of Nanoparticles by Polymers via Dissipative Particle Dynamics Method.

Patchy particles are often referred to colloidal particles with physically or chemically patterned surfaces. We investigated the patterning of nanoparticle grafted by polymers, mainly consisting of patchy structures with different numbers of patches ( Npatch) and core-shell structure using the dissipative particle dynamics (DPD) method in good or poor solvents based on the experiment research. Poor solvent, large nanoparticle, proper grafting density and medium polymer length contribute to the formation of patchy structure. We introduce the effective volume fraction as an indicator to distinguish the patchy structure from core-shell structure. The reversible transition between core-shell (in a good solvent) and patchy structure (in a poor solvent) and the dependency relationship between the nanoparticle diameter and grafting density in experiment are verified. Our results pave the way for preparing the colloids with well-defined patches. The anisotropic patchy particles can self-assemble into elaborate superstructures, which are potential blocking materials for drug delivery, sensors, and electronics.

Cryo-electron microscopy study of insect cell-expressed enterovirus 71 and coxsackievirus a16 virus-like particles provides a structural basis for vaccine development.

UNLABELLED: Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two most common etiological agents responsible for the epidemics of hand, foot, and mouth disease (HFMD), a childhood illness with occasional severe neurological complications. A number of vaccine candidates against EV71 or CA16 have been reported; however, no vaccine is currently available for clinical use. Here, we generated a secreted version of EV71 and CA16 virus-like particles (VLPs) using a baculovirus-insect cell expression system and reconstructed the three-dimensional (3D) structures of both VLPs by cryo-electron microscopy (cryo-EM) single-particle analysis at 5.2-Å and 5.5-Å resolutions, respectively. The reconstruction results showed that the cryo-EM structures of EV71 and CA16 VLPs highly resemble the recently published crystal structures for EV71 natural empty particles and CA16 135S-like expanded particles, respectively. Our cryo-EM analysis also revealed that the majority of previously identified linear neutralizing epitopes are well preserved on the surface of EV71 and CA16 VLPs. In addition, both VLPs were able to induce efficiently neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71- and CA16-associated HFMD. IMPORTANCE: The recent outbreaks of hand, foot, and mouth disease (HFMD) in the Asia Pacific region spurred the search for effective vaccines against EV71 and CA16 viruses, the two most common etiological agents responsible for HFMD. In this paper, we show that secreted versions of EV71 and CA16 VLPs generated in the baculovirus-insect cell expression system highly resemble the crystal structures of their viral conterparts and that the majority of previously identified linear neutralizing epitopes are well preserved on the VLP surfaces. In addition, the generated VLPs can efficiently induce neutralizing antibodies against various strains of EV71 and CA16 viruses in mouse immunization. These studies provide a structural basis for the development of insect cell-expressed VLP vaccines and for a potential bivalent VLP vaccine against both EV71- and CA16-associated HFMD.

Cryo-EM structures of infectious bursal disease viruses with different virulences provide insights into their assembly and invasion.

Infectious bursal disease virus (IBDV) causes a highly contagious immunosuppressive disease in chickens, resulting in significant economic losses. The very virulent IBDV strain (vvIBDV) causes high mortality and cannot adapt to cell culture. In contrast, attenuated strains of IBDV are nonpathogenic to chickens and can replicate in cell culture. Although the crystal structure of T = 1 subviral particles (SVP) has been reported, the structures of intact IBDV virions with different virulences remain elusive. Here, we determined the cryo-electron microscopy (cryo-EM) structures of the vvIBDV Gx strain and its attenuated IBDV strain Gt at resolutions of 3.3 Å and 3.2 Å, respectively. Compared with the structure of T = 1 SVP, IBDV contains several conserved structural elements unique to the T = 13 virion. Notably, the N-terminus of VP2, which is disordered in the SVP, interacts with the SF strand of VP2 from its neighboring trimer, completing the ß-sheet of the S domain. This interaction helps to form a contact network by tethering the adjacent VP2 trimers and contributes to the assembly and stability of the IBDV virion. Structural comparison of the Gx and Gt strains indicates that H253 and T284 in the VP2 P domain of Gt, in contrast to Gx, form a hydrogen bond with a positively charged surface. This suggests that the combined mutations Q253H/A284T and the associated structural electrostatic features of the attenuated Gt strain may contribute to adaptation to cell culture. Furthermore, a negatively charged groove in VP2, containing an integrin binding IDA motif that is critical for virus attachment, was speculated to play a functional role in the entry of IBDV.

Insect cell-expressed hemagglutinin with CpG oligodeoxynucleotides plus alum as an adjuvant is a potential pandemic influenza vaccine candidate.

Vaccination is the most effective method used to reduce the morbidity and mortality of influenza infections. However, as exemplified in the current swine-origin influenza virus (S-OIV) pandemic, the global manufacturing capacity of influenza vaccines is severely limited. In the present proof-of-concept study, we combined cell substrate selection and antigen engineering with adjuvant development to design a potential pandemic influenza vaccine candidate, in which CpG oligodeoxynucleotides (CpG-ODN) plus alum was used as a composite adjuvant to enhance the immunogenicity of insect cell-expressed recombinant hemagglutinin (rHA). Our candidate vaccine was found to be effective in inducing protective humoral as well as cellular immunity in mice and able to protect the immunized mice from related influenza virus challenge. If this candidate vaccine is validated in humans, vaccine development can be started immediately after the release of the first HA sequence of any pandemic influenza virus. Moreover, given the potential of large-scale manufacturing capacity of the recombinant antigen, in combination with the antigen-sparing effect of the composite adjuvant, this technology could be an invaluable asset in the fight against pandemic influenza.