Structural Effects of Cation Binding to DPPC Monolayers.

Ions at the two sides of the plasma membrane maintain the transmembrane potential, participate in signaling, and affect the properties of the membrane itself. The extracellular leaflet is particularly enriched in phosphatidylcholine lipids and under the influence of Na+, Ca2+, and Cl- ions. In this work, we combined molecular dynamics simulations performed using state-of-the-art models with vibrational sum frequency generation (VSFG) spectroscopy to study the effects of these key ions on the structure of dipalmitoylphosphatidylcholine. We used lipid monolayers as a proxy for membranes, as this approach enabled a direct comparison between simulation and experiment. We find that the effects of Na+ are minor. Ca2+, on the other hand, strongly affects the lipid headgroup conformations and induces a tighter packing of lipids, thus promoting the liquid condensed phase. It does so by binding to both the phosphate and carbonyl oxygens via direct and water-mediated binding modes, the ratios of which depend on the monolayer packing. Clustering analysis performed on simulation data revealed that changes in area per lipid or CaCl2 concentration both affect the headgroup conformations, yet their effects are anticorrelated. Cations at the monolayer surface also attract Cl-, which at large CaCl2 concentrations penetrates deep to the monolayer. This phenomenon coincides with a radical change in the VSFG spectra of the phosphate group, thus indicating the emergence of a new binding mode.

Properties of Lipid Models of Lung Surfactant Containing Cholesterol and Oxidized Lipids: A Mixed Experimental and Computational Study.

We introduce and study a multicomponent lipid film mimicking lipid composition of the human lung surfactant. It consists of phospholipids with various lipid headgroups and tail saturation. Furthermore, it includes cholesterol and oxidized lipids. Langmuir trough and fluorescence microscopy experiments are combined with fully atomistic molecular dynamics simulations. The considered lipid mixtures form complex interfacial films with properties modulated by lateral compression. Cholesterol laterally condenses, and oxidized lipids laterally expand the films; both types of molecules increase film miscibility. Oxidized lipids also alter the lipid-water interface enhancing film hydration; this effect can be partially reversed by cholesterol. Regarding presentation of different chemical moieties toward the aqueous subphase, the zwitterionic phosphatidylcholine groups dominate at the lipid-water interface, while both the negatively charged phosphatidylglycerol and hydroxyl group of cholesterol are less exposed. The investigated synthetic lipid-only mimic of the lung surfactant may serve as a basis for further studies involving nonlipid pulmonary surfactant components.

Binding of Divalent Cations to Insulin: Capillary Electrophoresis and Molecular Simulations.

In the present study, we characterize the binding of divalent cations to insulin in aqueous salt solutions by means of capillary electrophoresis and molecular dynamics simulations. The results show a strong pH dependence. At low pH, at which all the carboxylate groups are protonated and the protein has an overall positive charge, all the cations exhibit only weak and rather unspecific interactions with insulin. In contrast, at close to neutral pH, when all the carboxylate groups are deprotonated and negatively charged, the charge-neutralizing effect of magnesium, calcium, and zinc, in particular, on the electrophoretic mobility of insulin is significant. This is also reflected in the results of molecular dynamics simulations showing accumulation of cations at the protein surface, which becomes smaller in magnitude upon effective inclusion of electronic polarization via charge rescaling.

The Partitioning of Small Aromatic Molecules to Air-Water and Phospholipid Interfaces Mediated by Non-Hydrophobic Interactions.

Phenylalanine has an important role both in normal biological function and in disease states such as phenylketonuria (PKU) and amyloid fibril diseases. Two crucial aspects of phenylalanine behavior in biological systems are its preferential partitioning into membranes and its propensity to cluster. In order to examine the intermolecular interactions that give rise to this behavior, the surface partitioning behavior was investigated for a series of molecules structurally related to phenylalanine (phenylglycine, phenylacetic acid, and tyrosine) both experimentally and by molecular dynamics simulations. Surface tension measurements were performed over time for aromatic solutions both in the presence and in the absence of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) monolayer films, which functioned as simple model membranes. The observed trends in surface activity defy simple predictions based on solubility and hydrophobicity. The possibility of clustering is investigated through a combination of Langmuir trough, nuclear magnetic resonance (NMR), fluorescence self-quenching, and mass spectroscopy measurements. It is concluded that clustering does not occur in solution to a significant extent for these molecules, but interfacial clustering is likely. An explanation for observed trends in surface activity is presented on the basis of cluster stability and molecular conformational flexibility.

Identification of Di(oxymethylene)glycol in the Raman Spectrum of Formaldehyde Aqueous Solutions by ab Initio Molecular Dynamics Simulations and Quantum Chemistry Calculations.

Di(oxymethylene)glycol forms in formaldehyde aqueous solutions by polymerization of methanediol. The structure and hydrogen bond interactions of di(oxymethylene)glycol with water were characterized by performing Car-Parrinello molecular dynamics simulations. The anharmonic vibrational frequencies of di(oxymethylene)glycol in solution were determined with ab initio calculations considering explicitly the hydrogen-bonded water molecules, while other interactions with solvent were described within a polarizable continuum model approach. The calculations allow for a detailed interpretation of the experimental Raman spectrum of formaldehyde aqueous solutions, leading to the assignment of the band at 920 cm(-1) to the symmetric CO stretching mode of di(oxymethylene)glycol.

Structural and spectroscopic properties of methanediol in aqueous solutions from quantum chemistry calculations and ab initio molecular dynamics simulations.

The structural, electronic, and spectroscopic properties of methanediol in aqueous solutions have been studied by a combined approach based on Car-Parrinello molecular dynamics simulations and ab initio calculations. The hydrogen bond interactions between the solute and water have been characterized, showing the important role of the solvent in the stabilization of the methanediol conformers in solution. First insights on the experimental vibrational spectra have been obtained by the analysis of the simulation results, with particular regard to the most prominent band at 1050 cm(-1) that has been attributed to both the symmetric and antisymmetric CO stretching modes. The assignment has been completed adopting both electric and mechanical anharmonic calculations considering the interactions with the solvent using a polarizable continuum model.