Search

The pressure stability of the first hydration shell of Y3+ ions in aqueous solution has been investigated by means of extended x-ray absorption fine-structure spectroscopy at the yttrium K-edge for...

RSC Advances 10(58), 35329 - 35340 (2020). doi:10.1039/D0RA07679A, Supramolecular assembly and PEGylation (attachment of a polyethylene glycol polymer chain) of peptides can be an effective strategy to develop antimicrobial peptides with increased stability, antimicrobial efficacy and hemocompatibility. However, how the self-assembly properties and PEGylation affect their lipid membrane interaction is still an unanswered question. In this work, we use state-of-the-art small angle X-ray and neutron scattering (SAXS/SANS) together with neutron reflectometry (NR) to study the membrane interaction of a series of multidomain peptides, with and without PEGylation, known to self-assemble into nanofibers. Our approach allows us to study both how the structure of the peptide and the membrane are affected by the peptide–lipid interactions. When comparing self-assembled peptides with monomeric peptides that are not able to undergo assembly due to shorter chain length, we found that the nanofibers interact more strongly with the membrane. They were found to insert into the core of the membrane as well as to absorb as intact fibres on the surface. Based on the presented results, PEGylation of the multidomain peptides leads to a slight net decrease in the membrane interaction, while the distribution of the peptide at the interface is similar to the non-PEGylated peptides. Based on the structural information, we showed that nanofibers were partially disrupted upon interaction with phospholipid membranes. This is in contrast with the considerable physical stability of the peptide in solution, which is desirable for an extended in vivo circulation time., Published by RSC Publishing, London

Self-assembly of amphiphilic polymers into micelles is an archetypical example of a "self-confined" system due to the formation of micellar cores with dimensions of a few nanometers. In this work, we investigate the chain packing and resulting shape of C-n-PEOx micelles with semicrystalline cores using small/wide-angle X-ray scattering (SAXS/WAXS), contrast-variation small-angle neutron scattering (SANS), and nuclear magnetic resonance spectroscopy (NMR). Interestingly, the n-alkyl chains adopt a rotator-like conformation and pack into prolate ellipses (axial ratio epsilon approximate to 0.5) in the "crystalline" region and abruptly arrange into a more spheroidal shape (e approximate to 0.7) above the melting point. We attribute the distorted spherical shape above the melting point to thermal fluctuations and intrinsic rigidity of the n-alkyl blocks. We also find evidence for a thin dehydrated PEO layer (

We investigate micelles formed by mixtures of n-alkyl-poly(ethylene oxide) block copolymers, Cn-PEO, with different alkyl block lengths in aqueous solution. This model system has previously been used to shed light on the interplay between exchange kinetics and crystallinity in self-assembling systems [König et al., Phys. Rev. Lett., 2019, 122, 078001]. Now we report on the structure and thermodynamics of these micelles by combining results from small-angle X-ray scattering, differential scanning calorimetry and volumetric measurements. We show that mixed micelles are formed despite the fact that length-mismatched n-alkanes of similar weights in bulk tend to demix below the crystallization temperature. Instead, the system exhibits similar properties as single-component micelles but with a modulated melting region. Interestingly, the melting point depression due to self-confinement within the micellar core can be approximately described by a generalized Gibbs-Thomson equation, similar to single-component micelles [Zinn et al. Phys. Rev. Lett., 2014, 113, 238305]. Furthermore, we find a novel scaling law for these micelles where, at least for larger n, the aggregation number scales with the third power of the length of the hydrophobic block, Nagg ∝ n3. Possibly, there might be a cross-over from the conventional Nagg ∝ n2 behaviour around n ≈ 19. However, the reason for such a transition as well as the strong n dependence remains a challenge and requires more theoretical work.

In the present work two subclasses of the human antibody Immunoglobulin G (IgG) have been investigated by Small-Angle X-ray Scattering under high hydrostatic pressures up to 5kbar. It is shown that IgG adopts a symmetric T-shape in solution which differs significantly from available crystal structures. Moreover, high-pressure experiments verify the high stability of the IgG molecule. It is not unfolded by hydrostatic pressures of up to 5kbar but a slight increase of the radius of gyration was observed at elevated pressures.

Telechelic polymers contain two chain ends that are able to promote self-assembly into "flowerlike" or interconnected micellar structures. Here, we investigate the molecular exchange kinetics of such micelles using time-resolved small-angle neutron scattering. We show that the activation energies of monofunctional and telechelic chain exchange are identical. This demonstrates that the two chain ends are not simultaneously released in a single event. Instead, the results show that, contrary to regular micelles, the kinetics occurs in a multistep process involving a collision-induced single-molecule exchange mechanism where the exchange rate is directly proportional to the polymer concentration. We show that this novel mechanism can be quantitatively explained by a simple kinetic model.

Molecular exchange processes are important equilibration and transport mechanisms in both synthetic and biological self-assembled systems such as micelles, vesicles, and membranes. Still, these processes are not entirely understood, in particular the effect of crystallinity and the interplay between cooperative melting processes and chain exchange. Here we focus on a set of simple polymer micelles formed by binary mixtures of poly(ethylene oxide)-mono-$n$-alkyl-ethers (${\mathrm{C}}_{n}\text{\ensuremath{-}}\mathrm{PEO}5$) which allows the melting point to be tuned over a wide range. We show that the melting transition is cooperative in the confined 4--5 nm micellar core, whereas the exchange process is widely decoupled and unimeric in nature. As confirmed by differential scanning calorimetry, the total activation energy for ejecting a molecule out of the micellar core below the melting point is the sum of the enthalpy of fusion and the corresponding activation energy in the melt state. This suggests that a ``local, single-chain melting process'' preludes the molecular diffusion out of the micelle during chain exchange.

The influence of natural cosolvent mixtures on the pressure-dependent structure and protein-protein interaction potential of dense protein solutions is studied and analyzed using small-angle X-ray scattering in combination with a liquid-state theoretical approach. The deep-sea osmolyte trimethylamine-N-oxide is shown to play a crucial and singular role in its ability to not only guarantee sustainability of the native protein's folded state under harsh environmental conditions, but it also controls water-mediated intermolecular interactions at high pressure, thereby preventing contact formation and hence aggregation of proteins.

We present results from small-angle X-ray scattering and turbidity measurements on the effect of high hydrostatic pressure on the phase behavior of dense lysozyme solutions in the liquid-liquid phase separation region, and characterize the underlying intermolecular protein-protein interactions as a function of temperature and pressure under charge-screening conditions (0.5 M NaCl). A reentrant liquid-liquid phase separation region is observed at elevated pressures, which may originate in the pressure dependence of the solvent-mediated protein-protein interaction. A temperature-pressure-concentration phase diagram was constructed for highly concentrated lysozyme solutions over a wide range of temperatures, pressures and protein concentrations including the critical region of the liquid-liquid miscibility gap.