Interaction between Alzheimer's Aβ(25–35) peptide and phospholipid bilayers: The role of cholesterol

AbstractThere is mounting evidence that the lipid matrix of neuronal cell membranes plays an important role in the accumulation of β-amyloid peptides into senile plaques, one of the hallmarks of Alzheimer's disease (AD). With the aim to clarify the molecular basis of the interaction between amyloid peptides and cellular membranes, we investigated the interaction between a cytotoxic fragment of Aβ(1–42), i.e., Aβ(25–35), and phospholipid bilayer membranes. These systems were studied by Electron Paramagnetic Resonance (EPR) spectroscopy, using phospholipids spin-labeled on the acyl chain. The effect of inclusion of charged phospholipids or/and cholesterol in the bilayer composition was considered in relation to the peptide/membrane interaction. The results show that Aβ(25–35) inserts in bilayers formed by the zwitterionic phospholipid dilauroyl phosphatidylcholine (DLPC), positioning between the outer part of the hydrophobic core and the external hydrophilic layer. This process is not significantly influenced by the inclusion of the anionic phospholipid phosphatidylglycerol (DLPG) in the bilayer, indicating the peptide insertion to be driven by hydrophobic rather than electrostatic interactions. Cholesterol plays a fundamental role in regulating the peptide/membrane association, inducing a membrane transition from a fluid-disordered to a fluid-ordered phase. At low cholesterol content, in the fluid-disordered phase, the insertion of the peptide in the membrane causes a displacement of cholesterol towards the more external part of the membrane. The crowding of cholesterol enhances its rigidifying effect on this region of the bilayer. Finally, the cholesterol-rich fluid-ordered membrane looses the ability to include Aβ(25–35)

Binary Mutual Diffusion Coefficients of Isoniazid Aqueous Solutions at (298.15 and 310.15) K

Binary mutual diffusion coefficients measured by the Taylor dispersion method in two different laboratories (University of Naples, Federico II, Italy, and University of Coimbra, Portugal) are reported for aqueous solutions of isoniazid at concentrations from (0.000 to 0.100) mol·dm−3 and at two temperatures (298.15 and 310.15) K. The hydrodynamic radii for the isoniazid in aqueous solution are calculated from the experimental results. In addition, the Hartley equation and the experimental diffusion coefficients are used to estimate activity coefficients for aqueous isoniazid at both temperature

Idrogeli modificati di PVA: studio del comportamento di fase del PVA in presenza di sali semplici e polimeri

Il poli(vinilalcol) PVA atattico è il polimero idrosolubile sintetico più prodotto negli Stati Uniti ed in Giappone, a causa delle svariate potenzialità applicative che vanno dall’impiego nell’industria tessile alla produzione di membrane per gli imballaggi. Tra le principali caratteristiche del PVA va menzionato il carattere semicristallino nonostante la sua scarsa stereoregolarità, ed una forte tendenza a formare legami idrogeno intra ed intermolecolari a causa della massiccia presenza dei gruppi sulle sue catene. Inoltre le soluzioni acquose di PVA possono dare luogo alla formazione termoreversibile di idrogeli, sotto opportune condizioni. Fin dai primi lavori pionieristici di Pines and Prins, è stato proposto che una separazione di fase delle soluzioni acquose in una fase più ricca di polimero ed un’altra più ricca di solvente fosse alla base della formazione di idrogeli in soluzioni acquose diluite. Komatsu, investigando la relazione tra la gelificazione e la separazione di fase delle soluzioni acquose di PVA in un ampio intervallo di concentrazioni e temperature, ha ottenuto un diagramma di fase, trovando che la formazione dell’idrogelo è determinata dalla segregazione di fase; consistentemente con i risultati di Pines e Prins, la gelificazione parte con la formazione di legami idrogeno seguita dalla cristallizzazione di parte delle catene di PVA. Il ruolo della separazione di fase liquido-liquido nella gelificazione del PVA è stato anche investigato da Wu che ha descritto la struttura degli hydrogels di PVA in termini di un insieme di due fasi: una più ricca ed un’altra più povera di polimero. La dimensione dei domini ricchi di polimero è dell’ordine dei ed è responsabile dell’aspetto opaco degli idrogeli di PVA. Un metodo comunemente impiegato per preparare gli idrogeli di PVA consiste nell’aggiungere ad una soluzione acquosa di polimero sostanze addizionali come il dimetilsolfossido (DMSO). L’organizzazione strutturale degli idrogelo così ottenuti è stata indagata da Kanaya e Takeshita mediante misure di scattering neutronico ad alti e bassi angoli, ed esperimenti di light scattering. Le investigazioni di questi autori hanno mostrato che l’idrogelo consiste di piccole regioni cristalline (cristalliti) le cui dimensioni lineari sono dell’ordine di ~ 70Å, e le distanze dell’ordine di 150-200 Å. Inoltre questi idrogeli posseggono un’organizzazione supramolecolare dovuta alla presenza di domini ricchi in polimero, la cui dimensione è dell’ordine di qualche micron

Effect of glycerol on micelle formation by ionic and nonionic surfactants at 25°C

The effect of glycerol on the micellization of the cationic surfactant cetyltrimethylammonium bromide (CTAB) and of the ethoxylated nonionic surfactant Brij 58 has been investigated by various experimental techniques. For both surfactants the critical micellar concentration (cmc), determined by surface tension measurements, is almost unaffected by the presence of glycerol in the mixture; only at high glycerol concentrations (20% w/w) does the cmc significantly increase. The area per surfactant molecule at the air–solution interface, A, increases with increasing glycerol weight percentage, wg. Fluorescence quenching measurements indicate that the presence of glycerol induces a lowering of the aggregation number of both surfactants. The glycerol intradiffusion coefficient has been measured by the pulsed-gradient spin–echo NMR technique as a function of glycerol content at constant surfactant concentration. It is almost unaffected by the presence of the surfactants, indicating that no direct glycerol–surfactant interaction occurs in the mixture. The surfactant intradiffusion coefficient has been also measured. In the case of CTAB, it increases with increasing glycerol concentration, a reflection of the decreased aggregation number. For Brij 58, in spite of the lowering of the aggregation number, the surfactant intradiffusion coefficient decreases with increasing glycerol concentration, suggesting an increase of the intermicellar interaction. The experimental evidence shows that for both surfactants the micellization is affected by the presence of glycerol through an indirect, solvent-mediated mechanism. In the case of CTAB, the main effect of glycerol is a lowering of the medium dielectric constant, which enhances the electrostatic interactions in solution. In the case of Brij 58, the results can be interpreted in terms of a salting-out effect according to which glycerol competes with the surfactant for water molecules, causing a dehydration of the surfactant ethoxylic headgroup

Mutual and intradiffusion coefficients for the binary system n-decyl dimethyl phosphine oxide + water at 25 °C

Diffusion coefficients for the binary system n-decyl dimethyl phosphine oxide + water have been studied at 25 °C, with the aim to quantitatively describe the surfactant micellization process in aqueous medium. Accurate mutual diffusion coefficients have been measured by the Taylor dispersion technique. Intradiffusion coefficients of both components have been measured by the pulsed gradient spin echo (PGSE)-FT NMR technique. The data have been compared and interpreted in the framework of the equilibrium model of surfactant self-aggregation. Interpolation of the mutual diffusion coefficients has allowed us to estimate reliable values of the average number of surfactant molecules involved in the formation of a micellar aggregate and the constant of the equilibrium between these aggregates and surfactant unimers. Interpolation of water intradiffusion coefficients has allowed us to estimate the number of water molecules involved in the hydration of surfactants in unimeric and micellized form