Type Of Oligomer Research Articles

Single-Molecule Maps of Membrane Insertion by Amyloid-β Oligomers Predict Their Toxicity.

The interaction of small Amyloid-β (Aβ) oligomers with the lipid membrane is an important component of the pathomechanism of Alzheimer's disease (AD). However, oligomers are heterogeneous in size. How each type of oligomer incorporates into the membrane, and how that relates to their toxicity, is unknown. Here, we employ a single molecule technique called Q-SLIP (Quencher-induced Step Length Increase in Photobleaching) to measure the membrane insertion of each monomeric unit of individual oligomers of Aβ42, Aβ40, and Aβ40-F19-Cyclohexyl alanine (Aβ40-F19Cha), and correlate it with their toxicity. We observe that the N-terminus of Aβ42 inserts close to the center of the bilayer, the less toxic Aβ40 inserts to a shallower depth, and the least toxic Aβ40-F19Cha has no specific distribution. This oligomer-specific map provides a mechanistic representation of membrane-mediated Aβ toxicity and should be a valuable tool for AD research.

Efficient production of copolymerized PA6-based polymer fibers: Oligomer control and direct melt spinning

Synthesis of PA6-based polyester amides (PEAs) is the one of main way to expand the application of PA6. Due to the residual oligomers in the polymer matrix, PEAs are also difficult to achieve directly melt spinning similar to PA6. In this work, the molecular structure designable PEA synthesis method proposed in our previous work was further investigated to control the oligomer content control by end-amino shielding at open-loop stages and efficient de-volatilization at polycondensation stages. The effect of the molecular weight of PA6 segments on oligomer formation was also investigated. The results show that the oligomers, caprolactam, and cyclic dimer contents of PEAs are reduced to 2 wt%, 0.38–0.76 wt%, and 0.2–0.3 wt%, which is lower 75%, 85%, and 50% compared to industrially produced PA6, respectively. It indicates that the molecular weight of PA6 segments, in addition to affecting the physicochemical properties, can also thermodynamically enable regulation of the type of oligomer generated. By adjusting the chain segment structure and controlling the reaction conditions, all PEAs can be directly melting spinning (1200 m/min) and maintains good physical and chemical properties. At the same time, the substantial reduction in oligomers means that PEAs can completely eliminate post-processing such as hydrothermal extraction, fiber production time is shortened from more than 40 h (PA6) to less than 15 h and resource consumption is reduced by more than 30%. This oligomer control method is also applicable to functional PA6, which lays the foundation for efficient and sustainable industrial production of copolymerized PA6 functional fibers on a large scale.

Structural Expansion of Catalytic RNA Nanostructures through Oligomerization of a Cyclic Trimer of Engineered Ribozymes.

The multimolecular assembly of three-dimensionally structured proteins forms their quaternary structures, some of which have high geometric symmetry. The size and complexity of protein quaternary structures often increase in a hierarchical manner, with simpler, smaller structures serving as units for larger quaternary structures. In this study, we exploited oligomerization of a ribozyme cyclic trimer to achieve larger ribozyme-based RNA assembly. By installing kissing loop (KL) interacting units to one-, two-, or three-unit RNA molecules in the ribozyme trimer, we constructed dimers, open-chain oligomers, and branched oligomers of ribozyme trimer units. One type of open-chain oligomer preferentially formed a closed tetramer containing 12 component RNAs to provide 12 ribozyme units. We also observed large assembly of ribozyme trimers, which reached 1000 nm in size.

Structure specific neuro-toxicity of α-synuclein oligomer

Parkinson's disease (PD) is linked to α-synuclein (aS) aggregation and deposition of amyloid in the substantia nigra region of the brain tissues. In the current investigation we produced two distinct classes of aS oligomer of differed protein conformation, stability and compared their toxic nature to cultured neuronal cells. Lyophilized oligomer (LO) was produced in storage of aS at-20 °C for 7 days and it was enriched with loosely hold molten globule like structure with residues having preferences for α-helical conformational space. The size of the oligomer was 4–5.5 nm under AFM. This kind of oligomer exhibited potential toxicity towards neuronal cell lines and did not transform into compact β-sheet rich amyloid fiber even after incubation at 37 °C for several days. Formation of another type of oligomer was often observed in the lag phase of aS fibrillation that often occurred at an elevated temperature (37 °C). This kind of heat induced oligomer (IO) was more hydrophobic and relatively less toxic to neuronal cells compared to lyophilized oligomer (LO). Importantly, initiation of hydrophobic zipping of aS caused the transformation of IO into thermodynamically stable β-sheet rich amyloid fibril. On the other hand, the presence of molten globule like conformation in LO, rendered greater toxicity to cultured neuronal cells.

Solution Structure of the dATP-Inactivated Class I Ribonucleotide Reductase From Leeuwenhoekiella blandensis by SAXS and Cryo-Electron Microscopy.

The essential enzyme ribonucleotide reductase (RNR) is highly regulated both at the level of overall activity and substrate specificity. Studies of class I, aerobic RNRs have shown that overall activity is downregulated by the binding of dATP to a small domain known as the ATP-cone often found at the N-terminus of RNR subunits, causing oligomerization that prevents formation of a necessary α2β2 complex between the catalytic (α2) and radical generating (β2) subunits. In some relatively rare organisms with RNRs of the subclass NrdAi, the ATP-cone is found at the N-terminus of the β subunit rather than more commonly the α subunit. Binding of dATP to the ATP-cone in β results in formation of an unusual β4 tetramer. However, the structural basis for how the formation of the active complex is hindered by such oligomerization has not been studied. Here we analyse the low-resolution three-dimensional structures of the separate subunits of an RNR from subclass NrdAi, as well as the α4β4 octamer that forms in the presence of dATP. The results reveal a type of oligomer not previously seen for any class of RNR and suggest a mechanism for how binding of dATP to the ATP-cone switches off catalysis by sterically preventing formation of the asymmetrical α2β2 complex.

Quantitative analysis of weakly bound insulin oligomers in solution using polarized multidimensional fluorescence spectroscopy

Being able to measure the size and distribution of oligomers in solution is a critical issue in the manufacture and stability of insulin and other protein formulations. Measuring oligomers reliably can however be complicated, due to their fragile self-assembled structures, which are held together by weak forces. This can cause issues in chromatographic based methods, where dissociation or re-equilibration of oligomer populations can occur e.g. upon dilution in a different eluting buffer, but also for light scattering based methods like dynamic light scattering (DLS) where the size difference involved (often less than a factor 3) does not allow mixtures of oligomers to be resolved. Intrinsic fluorescence offers an attractive alternative as it is non-invasive, sensitive but also because it contains scattered light when implemented via excitation emission matrix (EEM) measurements, that is sensitive to changes in particle size.Here, using insulin at formulation level concentrations, we show for the first time how EEM can both discriminate and quantify the proportion of oligomeric states in solution. This was achieved by using the Rayleigh scatter (RS) band and the fluorescence signal contained in EEM. After validating size changes with DLS, we show in particular how the volume under the RS band correlated linearly with protein/oligomer molecular weight, in agreement with the Debye-Zimm relationship. This was true for the RS data from both EEM and polarized EEM (pEEM) measurements, the latter providing a stronger scatter signal, more sensitive to particle size changes.The fluorescence signal was then used with multivariate curve resolution (MCR) to quantify more precisely the soluble oligomer composition of insulin solutions. In conditions that promoted the formation of mainly one type of oligomer (monomer, dimer, or hexamer), pEEM-MCR helped identify the presence of small amounts of other oligomeric forms, while in conditions that were previously said to favour the insulin tetramer, we show that in the presence of zinc, these insulin samples were instead a heterogenous mixture composed of mostly dimers and hexamers. These MCR results correlated in all cases with the observed discrimination by principal component analysis (PCA), and deviations observed in the RS data. In conclusion, using pEEM scatter and emission components with chemometric data analysis provides a unique analytical method for characterising and monitoring changes in the soluble oligomeric state of proteins.

Ca10Na10[Te9O42](H2O): a hydrothermally synthesized quaternary tellurium(vi) oxide containing edge-sharing octahedral trimers.

A new tellurium(vi) oxycompound, Ca10Na10[Te9O42](H2O), was synthesized by a high-temperature, high-pressure hydrothermal reaction at 550 °C, its structure determined by single-crystal X-ray diffraction, and further characterized by energy dispersive, infrared, and X-ray photoelectron spectroscopy. The compound crystallizes in the centrosymmetric trigonal space group R3[combining macron]c (no. 167) with a = 9.743(2), c = 66.337(13) Å, and Z = 6. The structure consists of discrete linear edge-sharing octahedral trimers with the composition Te3O1410-, which is a new type of finite Te-O oligomer with Te6+ only. The large complex anions form a hexagonal close-packed lattice with the octahedral and tetrahedral interstices being filled with Ca2+ and Na+ cations and water molecules. The octahedral trimers in every other h.c.p. layer rotate around the 31 screw axis for 120°; therefore the unit cell has a very long c axis. This work is one of the few examples of the synthesis of metal tellurates by supercritical hydrothermal techniques.

Universal Soluble Polymer Supports with Precisely Controlled Loading Capacity for Sequence‐Defined Oligomer Synthesis

ABSTRACTSoluble supports, with optimal molecular structures for iterative oligomer synthesis, were prepared by atom transfer radical copolymerization of styrene with Fmoc‐amino ethyl methacrylate. Size exclusion chromatography and nuclear magnetic resonance indicated formation of copolymers with controlled chain lengths, chain ends, dispersity, and comonomer compositions. These polymers were afterward subjected to two subsequent modifications steps: (a) the debromination of their ω‐chain ends via a tributyltin hydride treatment and (b) the removal of the Fmoc‐protecting groups in acidic conditions, thus leading to bromine‐free copolymers with a precise primary amine loading capacity. These universal amine‐containing precursors were then derived into a variety of functional supports. A glycine‐loaded Wang‐type soluble polystyrene support was prepared in two steps and tested for peptide synthesis as well as for the preparation of digital oligo(alkoxyamine amide)s. In both cases, it was possible to obtain uniform sequence‐defined oligomers as evidenced by electrospray ionization tandem mass spectrometry. However, each type of oligomer required specific experimental conditions and therefore soluble supports with an adapted loading capacity for optimal synthesis. Furthermore, the amine‐containing universal precursors were also transformed into soluble supports for iterative phosphoramidite chemistry. A support was specifically conceived for the iterative synthesis of abiotic digital oligo(phosphodiester)s and another one was designed for oligonucleotide synthesis. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 403–410

Gain-of-function variants of FtsA form diverse oligomeric structures on lipids and enhance FtsZ protofilament bundling.

Escherichia coli requires FtsZ, FtsA and ZipA proteins for early stages of cell division, the latter two tethering FtsZ polymers to the cytoplasmic membrane. Hypermorphic mutants of FtsA such as FtsA* (R286W) map to the FtsA self-interaction interface and can bypass the need for ZipA. Purified FtsA forms closed minirings on lipid monolayers that antagonize bundling of FtsZ protofilaments, whereas FtsA* forms smaller oligomeric arcs that enable bundling. Here, we examined three additional FtsA*-like mutant proteins for their ability to form oligomers on lipid monolayers and bundle FtsZ. Surprisingly, all three formed distinct structures ranging from mostly arcs (T249M), a mixture of minirings, arcs and straight filaments (Y139D) or short straight double filaments (G50E). All three could form filament sheets at higher concentrations with added ATP. Despite forming these diverse structures, all three mutant proteins acted like FtsA* to enable FtsZ protofilament bundling on lipid monolayers. Synthesis of the FtsA*-like proteins in vivo suppressed the toxic effects of a bundling-defective FtsZ, exacerbated effects of a hyper-bundled FtsZ, and rescued some thermosensitive cell division alleles. Together, the data suggest that conversion of FtsA minirings into any type of non-miniring oligomer can promote progression of cytokinesis through FtsZ bundling and other mechanisms.

β-Carboxysome bioinformatics: identification and evolution of new bacterial microcompartment protein gene classes and core locus constraints.

Carboxysomes are bacterial microcompartments (BMCs) that enhance CO2 fixation in all cyanobacteria. Structurally, carboxysome shell proteins are classified according to the type of oligomer formed: hexameric (BMC-H), trimeric (BMC-T) and pentameric (BMC-P) proteins. To understand the forces driving the evolution of the carboxysome shell, we conducted a bioinformatic study of genes encoding β-carboxysome shell proteins, taking advantage of the recent large increase in sequenced cyanobacterial genomes. In addition to the four well-established BMC-H (CcmK1-4) classes, our analysis reveals two new CcmK classes, which we name CcmK5 and CcmK6. CcmK5 is phylogenetically closest to CcmK3 and CcmK4, and the ccmK5 gene is found only in genomes lacking ccmK3 and ccmk4 genes. ccmK6 is found predominantly in heterocyst-forming cyanobacteria. The gene encoding the BMC-T homolog CcmO is associated with the main carboxysome locus (MCL) in only 60% of all species. We find five evolutionary origins of separation of ccmO from the MCL. Transcriptome analysis demonstrates that satellite ccmO genes, in contrast to MCL-associated ccmO genes, are never co-regulated with other MCL genes. The dispersal of carboxysome shell genes across the genome allows for distinct regulation of their expression, perhaps in response to changes in environmental conditions.

Femtosecond Laser-Controlled Tip-to-Tip Assembly and Welding of Gold Nanorods.

Directed assembly of gold nanorods through the use of dithiolated molecular linkers is one of the most efficient methodologies for the morphologically controlled tip-to-tip assembly of this type of anisotropic nanocrystals. However, in a direct analogy to molecular polymerization synthesis, this process is characterized by difficulties in chain-growth control over nanoparticle oligomers. In particular, it is nearly impossible to favor the formation of one type of oligomer, making the methodology hard to use for actual applications in nanoplasmonics. We propose here a light-controlled synthetic procedure that allows obtaining selected plasmonic oligomers in high yield and with reaction times in the scale of minutes by irradiation with low fluence near-infrared (NIR) femtosecond laser pulses. Selective inhibition of the formation of gold nanorod n-mers (trimers) with a longitudinal localized surface plasmon in resonance with a 800 nm Ti:sapphire laser, allowed efficient trapping of the (n – 1)-mers (dimers) by hot spot mediated photothermal decomposition of the interparticle molecular linkers. Laser irradiation at higher energies produced near-field enhancement at the interparticle gaps, which is large enough to melt gold nanorod tips, offering a new pathway toward tip-to-tip welding of gold nanorod oligomers with a plasmonic response at the NIR. Thorough optical and electron microscopy characterization indicates that plasmonic oligomers can be selectively trapped and welded, which has been analyzed in terms of a model that predicts with reasonable accuracy the relative concentrations of the main plasmonic species.

Monodisperse Conjugated Polymer Particles via Heck Coupling—A Kinetic Study to Unravel Particle Formation in Step-Growth Dispersion Polymerization

Palladium-catalyzed cross-coupling dispersion polymerizations follow a step-growth mechanism and deliver highly monodisperse particles. This is surprising, considering the high polydispersity usually inherent to classical polycondensations at high conversion. Here we present a novel Heck-type dispersion polymerization yielding fluorescent submicrometer particles with an extremely narrow size distribution. We investigate the kinetics of the dispersion polymerization to unravel the mechanism behind the formation of monodisperse particles. We find that, at medium conversion, only one type of oligomer forms nuclei for the particles. These seed particles phase separate from solution at a critical molecular weight. Oligomers, reaching the critical molecular weight for dissolution after this initial nucleation event, condensate onto the existing nuclei, leading to uniform growth of the particles. Higher molecular weight material is obtained toward high conversion by coupling reactions inside of the particles. Th...

SAXS fingerprints of aldehyde dehydrogenase oligomers.

Enzymes of the aldehyde dehydrogenase (ALDH) superfamily catalyze the nicotinamide adenine dinucleotide-dependent oxidation of aldehydes to carboxylic acids. ALDHs are important in detoxification of aldehydes, amino acid metabolism, embryogenesis and development, neurotransmission, oxidative stress, and cancer. Mutations in genes encoding ALDHs cause metabolic disorders, including alcohol flush reaction (ALDH2), Sjögren–Larsson syndrome (ALDH3A2), hyperprolinemia type II (ALDH4A1), γ-hydroxybutyric aciduria (ALDH5A1), methylmalonic aciduria (ALDH6A1), pyridoxine dependent epilepsy (ALDH7A1), and hyperammonemia (ALDH18A1). We previously reported crystal structures and small-angle X-ray scattering (SAXS) analyses of ALDHs exhibiting dimeric, tetrameric, and hexameric oligomeric states (Luo et al., Biochemistry 54 (2015) 5513–5522; Luo et al., J. Mol. Biol. 425 (2013) 3106–3120). Herein I provide the SAXS curves, radii of gyration, and distance distribution functions for the three types of ALDH oligomer. The SAXS curves and associated analysis provide diagnostic fingerprints that allow rapid identification of the type of ALDH oligomer that is present in solution. The data sets provided here serve as a benchmark for characterizing oligomerization of ALDHs.

Key factors in determining the arrangement of π-conjugated oligomers inside carbon nanotubes.

Density functional theory (DFT) calculations with dispersion corrections elucidated the key factors for determining the arrangement of π-conjugated oligomers inside a carbon nanotube. The current study considered methyl-terminated terfurans as guests inside a host tube; the results were compared with those obtained in previous studies for methyl-terminated terthiophenes inside a nanotube. DFT calculations found that the most important factor in determining the guest arrangement is the host-guest interactions arising from long-range CH-π and π-π interactions. In particular, the host-guest interactions play a crucial role in the arrangement of π-conjugated oligomers inside a larger-diameter tube: π-conjugated oligomers sit near the inner tube wall to maximize attractive host-guest interactions. Within a smaller-diameter tube, host-guest interactions, as well as guest-guest (interchain) interactions, are responsible for the guest arrangement. Then, stronger host-guest (weaker guest-guest) interactions are a major (minor) factor. The stronger host-guest interactions are sufficient to deform the inner π-conjugated oligomers. Due to the tube encapsulation, inner terfurans lose their planarity, leading to a weakening of the interchain interactions. In contrast, tube encapsulation induces terthiophenes to assume nearly planar structures, enhancing their interchain interactions. As a result, the magnitude of the interchain interactions is dependent on the type of inner oligomer. Reflecting the different interchain interactions, multimeric terfurans inside a nanotube exhibit molecular packings that are different from those of the corresponding terthiophenes. Considering the importance of the arrangement of inner π-conjugated oligomers to their electronic properties, nanotube containers can thus tune the properties of inner oligomers.

Effect of TiO2 nanoparticle additions on the conductivity of network polymer electrolytes for lithium power sources

Network copolymer electrolytes were synthesized from polyether (polyester) diacrylates with different structures and chain lengths of polyester diacrylate and polyethylene glycol diacrylate. The optimum matrix for ion transport in the electrolyte was formed from only one type of oligomer. The influence of TiO2 nanopowder additions (∼60 nm) on the conductivity of the copolymer electrolyte was studied. The addition of 10 wt % TiO2 led to an increase in the conductivity by an order of magnitude at 30°C; the effective activation energy decreased by 20%. At elevated temperatures, the mobility of polymer chains increased and the contribution of TiO2 nanoparticles in ion transport was only half of the order of magnitude of the conductivity at 100°C. The increase in the conductivity of the polymer electrolyte after the addition of TiO2 was presumably caused by the formation of a more mobile state of the lithium ion near the nanoparticle surface, as shown by pulsed field gradient (PFG) 7Li NMR.

Structural Similarities and Differences between Amyloidogenic and Non-Amyloidogenic Islet Amyloid Polypeptide (IAPP) Sequences and Implications for the Dual Physiological and Pathological Activities of These Peptides

IAPP, a 37 amino-acid peptide hormone belonging to the calcitonin family, is an intrinsically disordered protein that is coexpressed and cosecreted along with insulin by pancreatic islet β-cells in response to meals. IAPP plays a physiological role in glucose regulation; however, in certain species, IAPP can aggregate and this process is linked to β-cell death and Type II Diabetes. Using replica exchange molecular dynamics with extensive sampling (16 replicas per sequence and 600 ns per replica), we investigate the structure of the monomeric state of two species of aggregating peptides (human and cat IAPP) and two species of non-aggregating peptides (pig and rat IAPP). Our simulations reveal that the pig and rat conformations are very similar, and consist of helix-coil and helix-hairpin conformations. The aggregating sequences, on the other hand, populate the same helix-coil and helix-hairpin conformations as the non-aggregating sequence, but, in addition, populate a hairpin structure. Our exhaustive simulations, coupled with available peptide-activity data, leads us to a structure-activity relationship (SAR) in which we propose that the functional role of IAPP is carried out by the helix-coil conformation, a structure common to both aggregating and non-aggregating species. The pathological role of this peptide may have multiple origins, including the interaction of the helical elements with membranes. Nonetheless, our simulations suggest that the hairpin structure, only observed in the aggregating species, might be linked to the pathological role of this peptide, either as a direct precursor to amyloid fibrils, or as part of a cylindrin type of toxic oligomer. We further propose that the helix-hairpin fold is also a possible aggregation prone conformation that would lead normally non-aggregating variants of IAPP to form fibrils under conditions where an external perturbation is applied. The SAR relationship is used to suggest the rational design of therapeutics for treating diabetes.

Divergent Mechanisms in Amyloid Formation Controlled by Critical Points

The aggregation of amyloidogenic proteins is infamous for being highly chaotic, with small variations in conditions leading to large changes in aggregation rates. We present experimental evidence that the origin of this phenomenom for a broad variety of amyloidogneic oligomers is related to the critical concentration for the formation of particular type of prefibrillar oligomer. Using chemical probes and real time solution NMR, we show that oligomers of this type reversibly form at sharply defined critical concentrations and temperatures in a manner similar to a phase transition. Similarly, the kinetics of fiber formation also show strong non-linearity near these critical points. For some amyloidogenic proteins such as IAPP, the pathway of amyloid formation switches as the critical point is approached, with aggregation initiating at different regions of the protein above and below the critical point. We also show that part of the effect of some inhibitors on amyloid aggregation is to abolish or shift the critical concentration, and map the interface between monomeric IAPP and Aβ and these aggregates.

Synthesis and Characterization of Thiol-Ene Functionalized Siloxanes and Evaluation of their Crosslinked Network Properties.

Three types of linear thiol-functionalized siloxane oligomers and three types of ene-functionalized oligomers were synthesized and subsequently photopolymerized. Within each type of thiol-functionalized oligomer, the ratio of mercaptan repeat units to non-reactive phenyl repeat units was varied to manipulate both the crosslink density and the degree of secondary interactions through pi-pi stacking. Similarly, the repeat units of the three ene-functionalized oligomers are composed of allyl-functional monomers, benzene-functional monomers, and octyl-functional monomers in varying ratios of benzene:octyl but with a constant fraction of allyl moieties. The structural composition of the siloxane oligomers plays a pivotal role in the observed material properties of networks formed through thiol-ene photopolymerization. Networks with a high concentration of thiol functionalities exhibit higher rubbery moduli, ultimate strengths, and Young's moduli than networks with lower thiol concentrations. Moreover, the concentration of functionalities capable of participating in secondary interactions via hydrogen bonding or pi-pi stacking directly impacts the network glass transition temperature and elasticity. The combination of low crosslink density and high secondary interactions produces networks with the greatest toughness. Finally, the fraction of octyl repeats correlates with the hydrophobic nature of the network.

Conformational Differences between Two Amyloid β Oligomers of Similar Size and Dissimilar Toxicity

Several protein conformational disorders (Parkinson and prion diseases) are linked to aberrant folding of proteins into prefibrillar oligomers and amyloid fibrils. Although prefibrillar oligomers are more toxic than their fibrillar counterparts, it is difficult to decouple the origin of their dissimilar toxicity because oligomers and fibrils differ both in terms of structure and size. Here we report the characterization of two oligomers of the 42-residue amyloid β (Aβ42) peptide associated with Alzheimer disease that possess similar size and dissimilar toxicity. We find that Aβ42 spontaneously forms prefibrillar oligomers at Aβ concentrations below 30 μm in the absence of agitation, whereas higher Aβ concentrations lead to rapid formation of fibrils. Interestingly, Aβ prefibrillar oligomers do not convert into fibrils under quiescent assembly conditions but instead convert into a second type of oligomer with size and morphology similar to those of Aβ prefibrillar oligomers. Strikingly, this alternative Aβ oligomer is non-toxic to mammalian cells relative to Aβ monomer. We find that two hydrophobic peptide segments within Aβ (residues 16-22 and 30-42) are more solvent-exposed in the more toxic Aβ oligomer. The less toxic oligomer is devoid of β-sheet structure, insoluble, and non-immunoreactive with oligomer- and fibril-specific antibodies. Moreover, the less toxic oligomer is incapable of disrupting lipid bilayers, in contrast to its more toxic oligomeric counterpart. Our results suggest that the ability of non-fibrillar Aβ oligomers to interact with and disrupt cellular membranes is linked to the degree of solvent exposure of their central and C-terminal hydrophobic peptide segments.

Mechanical properties and thermal stability of ambient-cured thick polysiloxane coatings prepared by a sol–gel process of organoalkoxysilanes

Ambient-curable polysiloxane coatings were prepared by pre-hydrolysis/condensation of phenyltrimethoxysilane (PTMS) and dimethyldimethoxysilane (DMDMS) in the presence of ammonia solution and subsequently mixing with aminopropyltriethoxysilane (APS). The mechanical properties of coatings were thoroughly examined at both macro- and micro-level and the thermal stability of coatings was characterized by thermogravimetic analysis, both of which were correlated with coating composition and the hydrolysis/condensation degree of polysiloxane oligomer. It was found that pro-hydrolysis step is essential for fabrication of thick crack-free coatings (18–35μm). Higher DMDMS molar ratio, more APS dosage and lower hydrolysis/condensation degree of polysiloxane oligomer favor enhancing the hardness. Excellent impact resistance (50cmkg) of coatings was obtained at 5% and 10% APS dosage, despite of the type and structure of polysiloxane oligomer. Whatever, the best scratch resistance of coatings was attained using the polysiloxane oligomer, prepared at PTMS-to-DMDMS molar ratio of 2:8 and water-to-precursor molar ratio of 1:1, and 5% APS dosage. The polysiloxane coatings exhibit high thermal stability, however, which strongly depends on the coating composition.