Interfacial Properties and Monolayer Collapse of Alkyl Benzenesulfonate Surfactant Monolayers at the Decane-Water Interface from Molecular Dynamics Simulations.

The molecular structure of a surfactant molecule is known to have a great effect on the interfacial properties and the type of nanostructures formed. In this work, we have performed molecular dynamics simulations on six isomers of an alkyl benzenesulfonate surfactant to investigate the effect of the degree and position of aromatic substitution on the interfacial properties and on the collapse of the surfactant monolayer at a decane-water interface. The surface pressure of the monolayers was shown to increase with increasing surface coverage, until some of the monolayers become mechanically unstable and form large undulations. Shifting the primary alkyl chain of the surfactant from the para to the meta position was found to significantly affect the orientation of the surfactant head groups, while the attachment position of the benzene ring along the primary alkyl chain plays a greater role in the orientation of the surfactant tails. In general, to the extent considered in this work, our results suggest that additional alkyl substitution and meta substitution of the primary alkyl chains increase both the effectiveness and efficiency of the surfactants, and accelerate the onset of monolayer collapse. The interface was found to consist of an inner Helmholtz layer of partially dehydrated counterions in contact with the surfactant head groups, an outer Helmholtz layer of hydrated counterions, and a diffuse layer. The di- and trisubstituted surfactants formed nearly spherical swollen micelles encapsulating pure decane, which effectively solubilizes decane in water as a microemulsion. The monosubstituted surfactants formed elongated buds that protrude from the interface, but did not detach from the monolayer. To our knowledge, the role of aromatic substitution on interfacial properties has not been investigated by molecular simulations previously. The results from this work could provide insights to design improved surfactants by exploiting aromatic substitution to encapsulate material for drug delivery and other applications.

Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis.

The self-assembly of abnormally folded proteins into amyloid fibrils is a hallmark of many debilitating diseases, from Alzheimer's and Parkinson diseases to prion-related disorders and diabetes type II. However, the fundamental mechanism of amyloid aggregation remains poorly understood. Core sequences of four to seven amino acids within natural amyloid proteins that form toxic fibrils have been used to study amyloidogenesis. We recently reported a class of systematically designed ultrasmall peptides that self-assemble in water into cross-ß-type fibers. Here we compare the self-assembly of these peptides with natural core sequences. These include core segments from Alzheimer's amyloid-ß, human amylin, and calcitonin. We analyzed the self-assembly process using circular dichroism, electron microscopy, X-ray diffraction, rheology, and molecular dynamics simulations. We found that the designed aliphatic peptides exhibited a similar self-assembly mechanism to several natural sequences, with formation of α-helical intermediates being a common feature. Interestingly, the self-assembly of a second core sequence from amyloid-ß, containing the diphenylalanine motif, was distinctly different from all other examined sequences. The diphenylalanine-containing sequence formed ß-sheet aggregates without going through the α-helical intermediate step, giving a unique fiber-diffraction pattern and simulation structure. Based on these results, we propose a simplified aliphatic model system to study amyloidosis. Our results provide vital insight into the nature of early intermediates formed and suggest that aromatic interactions are not as important in amyloid formation as previously postulated. This information is necessary for developing therapeutic drugs that inhibit and control amyloid formation.

Natural tri- to hexapeptides self-assemble in water to amyloid beta-type fiber aggregates by unexpected alpha-helical intermediate structures.

Many fatal neurodegenerative diseases such as Alzheimer's, Parkinson, the prion-related diseases, and non-neurodegenerative disorders such as type II diabetes are characterized by abnormal amyloid fiber aggregates, suggesting a common mechanism of pathogenesis. We have discovered that a class of systematically designed natural tri- to hexapeptides with a characteristic sequential motif can simulate the process of fiber assembly and further condensation to amyloid fibrils, probably via unexpected dimeric α-helical intermediate structures. The characteristic sequence motif of the novel peptide class consists of an aliphatic amino acid tail of decreasing hydrophobicity capped by a polar head. To our knowledge, the investigated aliphatic tripeptides are the shortest ever reported naturally occurring amino acid sequence that can adopt α-helical structure and promote amyloid formation. We propose the stepwise assembly process to be associated with characteristic conformational changes from random coil to α-helical intermediates terminating in cross-ß peptide structures. Circular dichroism and X-ray fiber diffraction analyses confirmed the concentration-dependent conformational changes of the peptides in water. Molecular dynamics simulating peptide behavior in water revealed monomer antiparallel pairing to dimer structures by complementary structural alignment that further aggregated and stably condensed into coiled fibers. The ultrasmall size and the dynamic facile assembly process make this novel peptide class an excellent model system for studying the mechanism of amyloidogenesis, its evolution and pathogenicity. The ability to modify the properties of the assembled structures under defined conditions will shed light on strategies to manipulate the pathogenic amyloid aggregates in order to prevent or control aggregate formation.

Variation and decomposition of the partial molar volume of small gas molecules in different organic solvents derived from molecular dynamics simulations.

The partial molar volumes, V(i), of the gas solutes H2, CO, and CO2, solvated in acetone, methanol, heptane, and diethylether are determined computationally in the limit of infinite dilution and standard conditions. Solutions are described with molecular dynamics simulations in combination with the OPLS-aa force field for solvents and customized force field for solutes. V(i) is determined with the direct method, while the composition of V(i) is studied with Kirkwood-Buff integrals (KBIs). Subsequently, the amount of unoccupied space and size of pre-formed cavities in pure solvents is determined. Additionally, the shape of individual solvent cages is analyzed. Calculated V(i) deviate only 3.4 cm(3) mol(-1) (7.1%) from experimental literature values. Experimental V(i) variations across solutions are reproduced qualitatively and also quantitatively in most cases. The KBI analysis identifies differences in solute induced solvent reorganization in the immediate vicinity of H2 (<0.7 nm) and solvent reorganization up to the third solvation shell of CO and CO2 (<1.6 nm) as the origin of V(i) variations. In all solutions, larger V(i) are found in solvents that exhibit weak internal interactions, low cohesive energy density and large compressibility. Weak internal interactions facilitate solvent displacement by thermal solute movement, which enhances the size of solvent cages and thus V(i). Additionally, attractive electrostatic interactions of CO2 and the solvents, which do not depend on internal solvent interactions only, partially reversed the V(i) trends observed in H2 and CO solutions where electrostatic interactions with the solvents are absent. More empty space and larger pre-formed cavities are found in solvents with weak internal interactions, however, no evidence is found that solutes in any considered solvent are accommodated in pre-formed cavities. Individual solvent cages are found to be elongated in the negative direction of solute movement. This wake behind the moving solute is more pronounced in case of mobile H2 and in solvents with weaker internal interactions. However, deviations from a spherical solvent cage shape do not influence solute-solvent radial distribution functions after averaging over all solvent cage orientations and hence do not change V(i). Overall, the applied methodology reproduces V(i) and its variations reliably and the used V(i) decompositions identify the underlying reasons behind observed V(i) variations.

Insights into the structure of covalently bound fatty acid monolayers on a simplified model of the hair epicuticle from molecular dynamics simulations.

The epicuticle is the outermost layer of the human hair, and consists of a monolayer of fatty acids that is predominantly 18-methyleicosanoic acid (18-MEA) covalently bound to a protein matrix. Surprisingly, despite the clear scientific and industrial importance, the detailed molecular structure of this fatty acid layer is still poorly understood. In this work, we aim to gain insight into the structure of this so-called F-layer by performing molecular dynamics simulations on a simplified hair surface model consisting of a monolayer of 18-MEA covalently attached to graphene sheets at various separation distances. The relative free energy of the fatty acid layer was calculated as a function of separation distance in order to obtain the optimal packing density of the fatty acids. Conformational properties such as the thickness, tilt angle, and order parameter of the fatty acid layers were also calculated to characterize the structure of the F-layer. Simulations of the structurally similar eicosanoic acid (EA) were also performed as a comparison and to investigate the role of the anteiso-methyl side chain at the 18th position of 18-MEA. The degree of water penetration into the fatty acid layer at the various separation distances was also investigated. Our simulations suggest that the optimal spacing for the fatty acids is between 0.492 and 0.651 nm, in contrast to the generally accepted literature value of around 0.9-1.0 nm. This results in a packing density of between 0.21 and 0.37 nm(2) per fatty acid molecule and a thickness of around 2.01-2.64 nm. We also show that, at larger separation distances, the 18-MEA fatty acid provides a slightly better hydrophobic layer than the EA fatty acid, suggesting that the 18-MEA fatty acid may have been naturally selected to provide better protection for the hair when it loses some of the fatty acids due to daily wear and tear. To our knowledge, this is the first attempt to systematically investigate the hair surface structure and properties with molecular simulations.

Protein-like dynamics of polycarbonate polymers in water.

The dynamics of amphiphilic peptide-mimicking polycarbonate polymers are investigated, considering variations in polymer length, monomer sequence, and monomer modification. The polymers are simulated in aqueous solution with atomistic molecular dynamics simulations and an empirical force field. Various structural polymer properties, interaction strengths, and solvation free energies are derived. It is found that water is a less favorable solvent for these polymers than for peptides. Moreover, polymers readily adopt irreversibly a compact state that consists of a variety of distinct compact conformations that are adopted through frequent transitions. Furthermore, the polymers exhibit a strong propensity to form large aggregates. The driving forces for these processes appear to be a hydrophobic effect and more favorable polymer-solvent interactions of aggregates that overcome the otherwise strong mutual repulsion between the positively charged polymers. Replacing hydrophobic residues with polar side chains destabilizes the compact conformations of the polymers. Our results also indicate that the monomer sequence has little effect on the overall solvation properties of the polymer molecule. However, the sequence influences flexibility and compactness of the monomer in solution. Overall, the results of this work confirm the protein-like characteristics of these polymers and elucidate the role of single residues in influencing the structure and aggregation in aqueous solution.

Impact of ionic liquids in aqueous solution on bacterial plasma membranes studied with molecular dynamics simulations.

The impact of five different imidazolium-based ionic liquids (ILs) diluted in water on the properties of a bacterial plasma membrane is investigated using molecular dynamics (MD) simulations. Cations considered are 1-octyl-3-methylimidazolium (OMIM), 1-octyloxymethyl-3-methylimidazolium (OXMIM), and 1-tetradecyl-3-methylimidazolium (TDMIM), as well as the anions chloride and lactate. The atomistic model of the membrane bilayer is designed to reproduce the lipid composition of the plasma membrane of Gram-negative Escherichia coli. Spontaneous insertion of cations into the membrane is observed in all ILs. Substantially more insertions of OMIM than of OXMIM occur and the presence of chloride reduces cation insertions compared to lactate. In contrast, anions do not adsorb onto the membrane surface nor diffuse into the bilayer. Once inserted, cations are oriented in parallel to membrane lipids with cation alkyl tails embedded into the hydrophobic membrane core, while the imidazolium-ring remains mostly exposed to the solvent. Such inserted cations are strongly associated with one to two phospholipids in the membrane. The overall order of lipids decreased after OMIM and OXMIM insertions, while on the contrary the order of lipids in the vicinity of TDMIM increased. The short alkyl tails of OMIM and OXMIM generate voids in the bilayer that are filled by curling lipids. This cation induced lipid disorder also reduces the average membrane thickness. This effect is not observed after TDMIM insertions due to the similar length of cation alkyl chain and the fatty acids of the lipids. This lipid-mimicking behavior of inserted TDMIM indicates a high membrane affinity of this cation that could lead to an enhanced accumulation of cations in the membrane over time. Overall, the simulations reveal how cations are inserted into the bacterial membrane and how such insertions change its properties. Moreover, the different roles of cations and anions are highlighted and the fundamental importance of cation alkyl chain length and its functionalization is demonstrated.

Monte carlo simulations of micellization in model ionic surfactants: application to sodium dodecyl sulfate.

A lattice model for ionic surfactants with explicit counterions is proposed for which the micellization behavior can be accurately determined from grand canonical Monte Carlo simulations. The model is characterized by a few parameters that can be adjusted to represent various linear surfactants with ionic headgroups. The model parameters have a clear physical interpretation and can be obtained from experimental data unrelated to micellization, namely, geometric information and solubilities of tail segments. As a specific example, parameter values for sodium dodecyl sulfate were obtained by optimizing for the solubility of hydrocarbons in water and the structural properties of dodecane. The critical micelle concentration (cmc), average aggregation number, degree of counterion binding, and their dependence on temperature were determined from histogram reweighting grand canonical Monte Carlo simulations and were compared to experimental results. The model gives the correct trend and order of magnitude for all quantities but underpredicts the cmc and aggregation number. We suggest ways to modify the model that may improve agreement with experimental values.