Polypeptide- and Protein-Based Conjugate Nanoparticles via Aqueous Ring-Opening Polymerization-Induced Self-Assembly (ROPISA).

Protein-polymer conjugates and polymeric nanomaterials hold great promise in many applications including biomaterials, medicine, or nanoelectronics. In this work, the first polymerization-induced self-assembly (PISA) approach performed in aqueous medium enabling protein-polymer conjugates and nanoparticles entirely composed of amino acids is presented by using ring-opening polymerization (ROP). It is indeed shown that aqueous ring-opening polymerization-induced self-assembly (ROPISA) can be used with protein or peptidic macroinitiators without prior chemical modification and afford the simple preparation of nanomaterials with protein-like property, for example, to implement biomimetic thermoresponsivity in drug delivery.

The Role of Backbone Polarity on Aggregation and Conduction of Ions in Polymer Electrolytes.

The usual understanding in polymer electrolyte design is that an increase in the polymer dielectric constant results in reduced ion aggregation and therefore increased ionic conductivity. We demonstrate here that in a class of polymers with extensive metal-ligand coordination and tunable dielectric properties, the extent of ionic aggregation is delinked from the ionic conductivity. The polymer systems considered here comprise ether, butadiene, and siloxane backbones with grafted imidazole side-chains, with dissolved Li+, Cu2+, or Zn2+ salts. The nature of ion aggregation is probed using a combination of X-ray scattering, electron paramagnetic resonance (in the case where the metal cation is Cu2+), and polymer field theory-based simulations. Polymers with less polar backbones (butadiene and siloxane) show stronger ion aggregation in X-ray scattering compared to those with the more polar ether backbone. The Tg-normalized ionic conductivities were however unaffected by the extent of aggregation. The results are explained on the basis of simulations which indicate that polymer backbone polarity does impact the microstructure and the extent of ion aggregation but does not impact percolation, leading to similar ionic conductivity regardless of the extent of ion aggregation. The results emphasize the ability to design for low polymer Tg through backbone modulation, separately from controlling ion-polymer interaction dynamics through ligand choice.

Influence of pore morphology on the diffusion of water in triblock copolymer membranes.

Understanding the transport properties of water in self-assembled block copolymer morphologies is important for furthering the use of such materials as water-purifying membranes. In this study, we used coarse-grained dissipative particle dynamics simulations to clarify the influence of pore morphology on the self-diffusion of water in linear-triblock-copolymer membranes. We considered representative lamellar, cylindrical, and gyroid morphologies and present results for both the global and local diffusivities of water in the pores. Our results suggest that the diffusivity of water in the confined, polymer-coated pores differs from that in the unconfined bulk. Explicitly, in confinement, the mobility of water is reduced by the hydrodynamic friction arising from the hydrophilic blocks coating the pore walls. We demonstrate that in lamella and cylindrical morphologies, the latter effects can be rendered as a universal function of the pore size relative to the brush height of the hydrophilic blocks.

Nanoscale Archimedean Tilings Formed by 3-Miktoarm Star Terpolymer Thin Films.

3-Miktoarm star terpolymer architecture (3µ-ABC), consisting of three dissimilar polymer chains, A, B, and C connected at a junction point, provides a unique opportunity in the design of complex nanoscale patterns such as Archimedean tilings that are not accessible from linear ABC terpolymers. In this work, the synthesis and the self-assembly of 3-miktoarm star terpolymers, namely, polystyrene-arm-poly(2-vinylpyridine)-arm-polyisoprene (3µ-SPI) into Archimedean tiling patterns is described. Several 3µ-SPI terpolymers are produced via a mid-functional PS-b-P2VP, synthesized by sequential anionic polymerization, using a 1,1-diphenylethylene bearing a tert-butyldimethylsilyl-protected hydroxyl functionality as a core molecule. PI arms with different sizes are then linked to the deprotected hydroxyl function of the core molecule via a Steglich esterification. Solvent-annealed 3µ-SPI thin films exhibit nanoscale prisms arranged into a (4.6.12) Archimedean tiling pattern. Depending on the size of the low etch-resistant PI arm and the solvent selected to promote the self-assembly of 3µ-SPI thin films, the voided columns occupy the square or decagonal sites of the (4.6.12) pattern. The use of this (4.6.12) tiling produced for the first time from self-assembled 3µ-ABC thin films can be a promising route to build 2D photonic crystals having complete photonic band gaps, where the light propagation is completely prohibited.

Metallic Nanodot Patterns with Unique Symmetries Templated from ABC Triblock Terpolymer Networks.

Nanotemplates derived from the self-assembly of AB-type block copolymers provide an elegant route to achieve well-defined metallic dot arrays, even if the variety of pattern symmetries is restricted due to the limited number of structures offered by microphase separated diblock copolymers. A strategy that relies on the use of complex network structures accessible through the self-assembly of linear ABC-type terpolymers is presented for the formation of metallic nanodots arrays with "outside-the-box" symmetries. Patterned templates formed by the cubic Q214 and orthorhombic O70 network structures are used as excellent platforms to build well-ordered gold nanodot arrays with unique p3m1 and p2 symmetries, respectively. A simple yet efficient blending strategy is used to tune the critical dimensions of the p3m1 pattern while laterally ordered gold nanodot arrays are also demonstrated through a directed self-assembly approach. Such highly ordered gold nanodots with tunable particle dimensions and array periods, enabling the control of their plasmonic responses, are attractive probes for biological imaging.

Core-Shell Double Gyroid Structure Formed by Linear ABC Terpolymer Thin Films.

The synthesis and self-assembly in thin-film configuration of linear ABC triblock terpolymer chains consisting of polystyrene (PS), poly(2-vinylpyridine) (P2VP), and polyisoprene (PI) are described. For that purpose, a hydroxyl-terminated PS-b-P2VP (45 kg mol-1 ) building block and a carboxyl-terminated PI (9 kg mol-1 ) are first separately prepared by anionic polymerization, and then are coupled via a Steglich esterification reaction. This quantitative and metal-free catalyst synthesis route reveals to be very interesting since functionalization and purification steps are straightforward, and well-defined terpolymers are produced. A solvent vapor annealing (SVA) process is used to promote the self-assembly of frustrated PS-b-P2VP-b-PI chains into a thin-film core-shell double gyroid (Q230 , space group: Ia3¯d) structure. As terraces are formed within PS-b-P2VP-b-PI thin films during the SVA process under a CHCl3 vapor, different plane orientations of the Q230 structure ((211), (110), (111), and (100)) are observed at the polymer-air interface depending on the film thickness.

Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules.

Designing highly specific modulators of protein-protein interactions (PPIs) is especially challenging in the context of multiple paralogs and conserved interaction surfaces. In this case, direct generation of selective and competitive inhibitors is hindered by high similarity within the evolutionary-related protein interfaces. We report here a strategy that uses a semi-rational approach to separate the modulator design into two functional parts. We first achieve specificity toward a region outside of the interface by using phage display selection coupled with molecular and cellular validation. Highly selective competition is then generated by appending the more degenerate interaction peptide to contact the target interface. We apply this approach to specifically bind a single PDZ domain within the postsynaptic protein PSD-95 over highly similar PDZ domains in PSD-93, SAP-97 and SAP-102. Our work provides a paralog-selective and domain specific inhibitor of PSD-95, and describes a method to efficiently target other conserved PPI modules.

An innovative flow cytometry method to screen human scFv-phages selected by in vivo phage-display in an animal model of atherosclerosis.

Atherosclerosis is a chronic, progressive inflammatory disease that may develop into vulnerable lesions leading to thrombosis. This pathology is characterized by the deposition of lipids within the arterial wall and infiltration of immune cells leading to amplification of inflammation. Nowadays there is a rising interest to assess directly the molecular and cellular components that underlie the clinical condition of stroke and myocardial infarction. Single chain fragment variable (scFv)-phages issuing from a human combinatorial library were selected on the lesions induced in a rabbit model of atherosclerosis after three rounds of in vivo phage display. We further implemented a high-throughput flow cytometry method on rabbit protein extracts to individually test one thousand of scFv-phages. Two hundred and nine clones were retrieved on the basis of their specificity for atherosclerotic proteins. Immunohistochemistry assays confirmed the robustness of the designed cytometry protocol. Sequencing of candidates demonstrated their high diversity in VH and VL germline usage. The large number of candidates and their diversity open the way in the discovery of new biomarkers. Here, we successfully showed the capacity of combining in vivo phage display and high-throughput cytometry strategies to give new insights in in vivo targetable up-regulated biomarkers in atherosclerosis.

Archimedean Tilings and Hierarchical Lamellar Morphology Formed by Semicrystalline Miktoarm Star Terpolymer Thin Films.

3-Miktoarm star terpolymer architecture provides a window of opportunity in the design of complex "three-colored" patterns at the nanometer scale. Here, the directed self-assembly (DSA) of 3-miktoarm star terpolymer (poly(1,1-dimethyl silacyclobutane)-arm-polystyrene-arm-poly(d,l-lactide acid)) (PDMSB-arm-PS-arm-PLA, noted hereafter 3 µ-DSL) into a hierarchical lamellar morphology is described. Excellent orientational order has been achieved by templating the asymmetric hierarchical lamellar morphology with topographical substrates. Increasing the PLA volume fraction leads to the formation of a hexagonal [6.6.6] Archimedean tiling which coexists with a metastable square symmetry [4.8.8] tiling stabilized by the step between terraces. Stability of the [6.6.6] tiling over the [4.8.8] one is also demonstrated with GISAXS measurements.