Structural Biology: Parkin’s Serpentine Shape Revealed in the Year of the Snake

SummaryParkin is an E3 ubiquitin ligase, mutations in which are responsible for autosomal recessive juvenile parkinsonism. Recently, several structures of Parkin have been solved, revealing its serpentine shape and modes of auto-inhibition

Precise tuning of polymeric fiber dimensions to enhance the mechanical properties of alginate hydrogel matrices

Hydrogels based on biopolymers, such as alginate, are commonly used as scaffolds in tissue engineering applications as they mimic the features of the native extracellular matrix (ECM). However, in their native state, they suffer from drawbacks including poor mechanical performance and a lack of biological functionalities. Herein, we have exploited a crystallization-driven self-assembly (CDSA) methodology to prepare well-defined one-dimensional micellar structures with controlled lengths to act as a mimic of fibrillar collagen in native ECM and improve the mechanical strength of alginate-based hydrogels. Poly(ε-caprolactone)-b-poly(methyl methacrylate)-b-poly(N, N-dimethyl acrylamide) triblock copolymers were self-assembled into 1D cylindrical micelles with precise lengths using CDSA epitaxial growth and subsequently combined with calcium alginate hydrogel networks to obtain nanocomposites. Rheological characterization determined that the inclusion of the cylindrical structures within the hydrogel network increased the strength of the hydrogel under shear. Furthermore, the strain at flow point of the alginate-based hydrogel was found to increase with nanoparticle content, reaching an improvement of 37% when loaded with 500 nm cylindrical micelles. Overall, this study has demonstrated that one-dimensional cylindrical nanoparticles with controlled lengths formed through CDSA are promising fibrillar collagen mimics to build ECM scaffold models, allowing exploration of the relationship between collagen fiber size and matrix mechanical properties

Functional degradable polymers by radical ring-opening copolymerization of MDO and vinyl bromobutanoate : synthesis, degradability and post-polymerization modification

The synthesis of vinyl bromobutanoate (VBr), a new vinyl acetate monomer derivative obtained by the palladium-catalyzed vinyl exchange reaction between vinyl acetate (VAc) and 4-bromobutyric acid is reported. The homopolymerization of this new monomer using the RAFT/MADIX polymerization technique leads to the formation of novel well-defined and controlled polymers containing pendent bromine functional groups able to be modified via postpolymerization modification. Furthermore, the copolymerization of vinyl bromobutanoate with 2-methylene-1,3-dioxepane (MDO) was also performed to deliver a range of novel functional degradable copolymers, poly(MDO-co-VBr). The copolymer composition was shown to be able to be tuned to vary the amount of ester repeat units in the polymer backbone, and hence determine the degradability, while maintaining a control of the final copolymers’ molar masses. The addition of functionalities via simple postpolymerization modifications such as azidation and the 1,3-dipolar cycloaddition of a PEG alkyne to an azide is also reported and proven by 1H NMR spectroscopy, FTIR spectroscopy, and SEC analyses. These studies enable the formation of a novel class of hydrophilic functional degradable copolymers using versatile radical polymerization methods

Controlling the synthesis of degradable vinyl polymers by xanthate-mediated polymerization

The copolymerization of vinyl acetate (VAc) and 2-methylene-1,3-dioxepane (MDO), as well as the homopolymerization of MDO in the presence of a p-methoxyphenyl xanthate chain transfer agent (CTA) is reported and comparison of the homopolymerization of MDO with other known xanthates was also investigated. In depth investigation showed loss of the xanthate functionality was a result of Z-group fragmentation leading to the formation of carbonodithioate groups, as confirmed by 13C NMR spectroscopy. The use of the xanthate with a substituted phenyl Z-group drastically reduces fragmentation through the Z-group and hence significantly increases chain-end retention during the polymerization using the RAFT/MADIX technique. Post-polymerization modification of the chain-end of poly(MDO) was achieved by in situ aminolysis and base-catalyzed Michael addition of propargyl methacrylate onto the terminal thiol to form alkyne functional poly(MDO)

Shape effect of glyco-nanoparticles on macrophage cellular uptake and immune response

The shells of various poly(dl-lactide)-b-poly(acrylic acid) (PDLLA-b-PAA) spherical micelles and poly(l-lactide)-b-poly(acrylic acid) (PLLA-b-PAA) cylindrical micelles were functionalized with mannose to yield glyco-nanoparticles (GNPs) with different shapes and dimensions. All of these GNPs were shown to have good biocompatibility (up to 1 mg/mL). Cellular uptake experiments using RAW 264.7 have shown that the spherical GNPs were internalized to a much greater extent than the cylindrical GNPs and such a phenomenon was attributed to their different endocytosis pathways. It was demonstrated that spherical GNPs were internalized based on clathrin- and caveolin-mediated endocytosis while cylindrical GNPs mainly depended on clathrin-mediated endocytosis. We also found that longer cylindrical GNPs (Ln × Wn = 215 × 47 nm) can induce an inflammatory response (specifically interleukin 6) more efficiently than shorter cylindrical GNPs (Ln × Wn = 99 × 50 nm) and spherical GNPs (Dn = 46 nm)

Functional nanostructures by NiCCo-PISA of helical poly(aryl isocyanide) copolymers

Herein, we present a straightforward and versatile methodology to achieve functional polymeric nano-objects that contain helical cores. Nickel-catalysed coordination polymerisation-induced self-assembly (NiCCo-PISA) of helical poly(aryl isocyanide) amphiphilic diblock copolymers was..

Ring-opening polymerisation of alkyl-substituted ε-caprolactones:kinetic effects of substitution position†

Ring-opening polymerisation (ROP) of lactones has been proven as a powerful technique to generate polyesters with high levels of control over molar mass and polymer dispersity. However, the introduction of functional groups on the monomer ring structure can dramatically influence the ability of a monomer to undergo ROP. Therefore, understanding the structure–reactivity relationship of functional monomers is essential to gain access to materials with chemical functionality via direct polymerisation. Herein, we report how structural modifications of alkyl-substituted ε-caprolactones affected their reactivity towards the ring-opening of the functional monomer. We observed that the reactivity was strongly influenced by the substituent position, wherein the δ-substituted monomer exhibited the fastest polymerisation kinetics. In contrast, a substituent placement in the ε-position significantly reduced polymerisation time compared to other substituent positions. Moreover, the thermal properties of the resultant functional ε-polycaprolactones were investigated and showed no significant change in the thermal transitions. This demonstrates that functional caprolactone monomers with sterically demanding functional groups can still undergo direct ring-opening polymerisation and that careful positioning of these functional groups enables control of the rate of polymerisation, a crucial parameter to be considered for the design of new prospective functional monomers and their industrial applications