The structure of colloidosomes with tunable particle density: simulation vs experiment

Colloidosomes are created in the laboratory from a Pickering emulsion of water droplets in oil. The colloidosomes have approximately the same diameter and by choosing (hairy) particles of different diameters it is possible to control the particle density on the droplets. The experiment is performed at room temperature. The radial distribution function of the assembly of (primary) particles on the water droplet is measured in the laboratory and in a computer experiment of a fluid model of particles with pairwise interactions on the surface of a sphere.Comment: 16 pages, 2 tables, 7 figure

Advancing membrane biology with poly(styrene-co-maleic acid)-based native nanodiscs

CITATION: Overduin, M. & Klumperman, B. 2019. Advancing membrane biology with poly(styrene-co-maleic acid)-based native nanodiscs. European Polymer Journal, 110:63-68, doi:10.1016/j.eurpolymj.2018.11.015.The original publication is available at https://www.sciencedirect.com/science/article/pii/S0014305718311364ENGLISH ABSTRACT: The elucidation of the structures and interactions of proteins and lipids in intact biological membranes remains largely uncharted territory. However, this information is crucial for understanding how organelles are assembled and how transmembrane machines transduce signals. The challenge of seeing how lipids and proteins engage each other in vivo remains difficult but is being aided by a group of amphipathic copolymers that spontaneously fragment native membranes into native nanodiscs. Poly(styrene-co-maleic acid) (SMA) copolymers have proven adept at converting membranes, cells and tissues directly into SMA lipid particles (SMALPs), allowing endogenous lipid: protein complexes to be prepared and analyzed. Unlike other amphipathic polymers such as amphipols, SMALP formation requires no conventional detergents, which typically strip lipid molecules from proteins and can destabilize multimers. A collaborative community of hundreds of investigators known as the SMALP network has emerged to develop and apply new technologies and identify new challenges and design potential solutions. In this contribution, we review recent practices and progress, focusing on novel SMA copolymers, modifications, alternatives and mechanisms. In addition, a brief overview will be provided, with reference to the further contributions to this special issue on the SMALP technology.https://www.sciencedirect.com/science/article/pii/S0014305718311364https://www.sciencedirect.com/science/article/pii/S0014305718311364Publisher's versio

The assembly of p-aryl triazole foldamers into double and other super- helical structures

The assembly of poly(para-aryltriazoles) (pPATs), synthesized via Cu(I)-catalysed azide-alkyne cycloaddition, into highly ordered structures is investigated. Firstly, the assembly of the pPATs into double helical structures, as a function of solvent quality and side chain chirality, was studied. The solvents employed (DMF and water) induced changes in van der Waals forces and surface free energy thus influencing the order of the pPATs’ random coils into double helical structures. The observed double helical structures, assembly that was analyzed using ultraviolet-visible (UV-Vis) specroscopy, circular dichroism (CD) spectroscopy, scanning transmission electron microscopy (STEM) and confocal fluorescence imaging microscopy upon addition of 0 – 80% water into the pPATs’ random coils, exhibit stable morphologies stabilized by π-π stacking and hydrogen bonding at 80% water content. The pPATs exist as random coils at 10% water in DMF. At 40% water in DMF, the pPATs’ strands were observed to exist in a side-by-side orientation. The adjacent strands, side by side, intertwine into double helices and eventually stack as the amount of water is increased to 80%. The obtained results present a facile strategy for the fabrication of polymeric double helical structures with stable morphologies. The average diameter of the resulting one-handed and opposite handed double helical structures is about 200 nm, a pitch of 170 nm and an overall length of several micrometres. The assembly of the pPATs into ordered structures in the presence of a neutral organic template and anions was also assessed. Hydrophobic poly(γ-benzyl-L-glutamate) (PBLG) template was introduced at various concentrations and transition region of the pPATs (10% water in DMF). At this stage the PBLG template is CD inactive. The template modified the assembly mechanism to afford structures, which cannot be achieved in its absence. It disallows the organization of the pPATs into double helical structures. The pPATs strands thread around the template and stack into long tubules of up to 10 microns and irregular diameter. The irregular diameter is attributed to uneven threading of pPATs strands around the template at some sections. The sensitivity and binding ability of the pPAT system to halide ions such as F-, Cl- and Br- , which involves re-organization of the aryl-triazole bonds, is explored using NMR and UV-Vis and CD spectroscopies. Br- which induces the highest shift of the triazole C-H proton signal in the NMR analysis also shows the highest dynamic quenching of the pPATs’ UV-Vis and CD spectra. The UV-Vis and CD signals are linearly dependent on the concentration of the anions. This confirms non-aggregation assembly in the presence of anions. Conclusively, the pPATs interact with the bromide anion in aqueous solution, which consequently prevents the aggregation of the foldamers. Finally, using PATs with different amounts of chiral side chains, co-operativity among side chains that leads to transfer, propagation and amplification of chirality is confirmed. A non-linear dependence of the CD signal on the amount of chiral side chains was observed. Chiral amplification was observed as low as 1% of the chiral side chains. However, approximately 20% of the chiral side chains are needed to obtain half the intensity of the cotton effect exhibited by the homochiral pPAT

Synthesis, Structure and Crystallization Behavior of Amphiphilic Hetero-arm Molecular Brushes with Crystallizable Poly(ethylene oxide) and N-Alkyl Side Chains

Unformatted post-print version of the accepted articleA series of hetero-arm amphiphilic molecular brushes (AMBs) with poly(ethylene glycol) (PEG) and long chain n-alkyl side chains were synthesized via conventional free radical polymerization (FRP) of mainly 4-vinyl benzyl-PEG methyl ether and N-alkylmaleimide macromonomers. By varying PEG side chain degree of polymerization (D.P. = 12, 16 and 20) and n-alkyl chain lengths (C16 and C20), AMBs with varying combinations of side chain lengths were produced. This enabled the elucidation of the effect of side chain length on AMB phase behavior, semicrystalline morphologies and crystallization kinetics, via differential scanning calorimetry, polarized light optical microscopy and x-ray diffraction experiments. Calculations of segregation strength together with SAXS measurements indicate that all materials are probably phase segregated structure in the melt. Most of the AMB materials prepared were double crystalline, i.e., contained crystals from alkyl and PEG chains. AMB crystallization was constrained by AMB architecture, the frustration being most evident in AMBs with combinations of either low D.P.PEG, or short alkyl chain lengths. Large, well-developed spherulites, implying break-out crystallization from a weakly segregated melt, were only observed for the AMBs with the combination of the longest PEG chain (D.P. = 20) and longest alkyl chain length (C20). A peculiar behavior was found when spherulitic growth rates and overall crystallization rates of the PEG chains, within this particular AMB sample, were determined as a function of crystallization temperature. In both cases, a distinct minimum with decreasing temperature was observed, probably caused by the challenges encountered in crystal packing of the PEG side chains, tethered to an amorphous backbone, which also contained already crystallized C20 chains. This minimum is analogous to that observed in the crystallization of long chain n-alkanes, or high molar mass polyethylenes with bromine pendant groups that has been attributed to a self-poisoning effect; this is the first observation of this phenomenon in AMBs.This work is based on the research supported by the South African Research Chairs Initiative of the Department of Science and Technology (DST) and National Research Foundation (NRF) of South Africa (Grant No 46855). J.M. acknowledges support from the Provincial Council of Gipuzkoa under the program Fellow Gipuzkoa and “Fomento San Sebastián” in the framework program “Retorno del Talento Local” Donostia up! 2016. This work has received funding from the European Union´s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 778092, from MINECO, project: MAT2017-83014-C2-1-P and from the Basque Government through grant IT1309-19. We also thank ALBA Synchrotron facility for providing funding and beam time (proposal number: 2018082953)

Facile route to targeted, biodegradable polymeric prodrugs for the delivery of combination therapy for malaria

A facile synthetic methodology has been developed to prepare multifaceted polymeric prodrugs that are targeted, biodegradable, and nontoxic, and used for the delivery of combination therapy. This is the first instance of the delivery of the WHO recommended antimalarial combination of lumefantrine (LUM, drug 1) and artemether (AM, drug 2) via a polymeric prodrug. To achieve this, reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization of N-vinylpyrrolidone (NVP) was conducted using a hydroxy-functional RAFT agent, and the resulting polymer was used as the macroinitiator in the ring-opening polymerization (ROP) of α-allylvalerolactone (AVL) to synthesize the biodegradable block copolymer of poly(N-vinylpyrrolidone) and poly(α-allylvalerolactone) (PVP-b-PAVL). The ω-end thiol group of PVP was protected using 2,2′-pyridyldisulfide prior to the ROP, and was conveniently used to bioconjugate a peptidic targeting ligand. To attach LUM, the allyl groups of PVP-b-PAVL underwent oxidation to introduce carboxylic acid groups, which were then esterified with ethylene glycol vinyl ether. Finally, LUM was conjugated to the block copolymer via an acid-labile acetal linkage in a “click”-type reaction, and AM was entrapped within the hydrophobic core of the self-assembled aggregates to render biodegradable multidrug-loaded micelles with targeting ability for combination therapy.The South African Research Chairs Initiative of the Department of Science and Technology (DST), the National Research Foundation (NRF) of South Africa, SARCHI: Communities of Practice in Malaria Elimination and SARChI Research Chair UID 84627 and UID 84627.http://pubs.acs.org/journal/abseba2021-10-07hj2021BiochemistryGeneticsMicrobiology and Plant Patholog

Linear dichroism activity of chiral poly(p-Aryltriazole) foldamers

Controllable higher-order assembly is a central aim of macromolecular chemistry. An essential challenge to developing these molecules is improving our understanding of the structures they adopt under different conditions. Here, we demonstrate how flow linear dichroism (LD) spectroscopy is used to provide insights into the solution structure of a chiral, self-assembled fibrillar foldamer. Poly(para-aryltriazole)s fold into different structures depending on the monomer geometry and variables such as solvent and ionic strength. LD spectroscopy provides a simple route to determine chromophore alignment in solution and is generally used on natural molecules or molecular assemblies such as DNA and M13 bacteriophage. In this contribution, we show that LD spectroscopy is a powerful tool in the observation of self-assembly processes of synthetic foldamers when complemented by circular dichroism, absorbance spectroscopy, and microscopy. To that end, poly(para-aryltriazole)s were aligned in a flow field under different solvent conditions. The extended aromatic structures in the foldamer give rise to a strong LD signal that changes in sign and in intensity with varying solvent conditions. A key advantage of LD is that it only detects the large assemblies, thus removing background due to monomers and small oligomers