Raman spectroscopy for detecting supported planar lipid bilayers composed of ganglioside-GM1/sphingomyelin/cholesterol in the presence of amyloid-β

Abstract

The aggregation and fibril formation of amyloid β(Aβ) peptides onto a ganglioside-GM1-containing lipid membrane is a cause of neurodegenerative diseases. The mechanism of the initial binding and the conformational changes of Aβ on the membrane should be clarified. Fluorescence microscopy and Raman spectroscopy have been performed to investigate the supporting planar lipid bilayers (SPBs) composed of ganglioside-GM1, sphingomyelin and cholesterol. It is demonstrated that the SPBs are in a liquid-crystalline state when placed on mica, and increasing the amount of ganglioside-GM1 can decrease the lateral interaction between the acyl chains of the SPBs. It has been found that Aβ(1-40) initially interacts with the galactose ring of the ganglioside-GM1 head group, leading to its binding and gradual aggregation on the membrane surface. The obvious change observed in Raman spectroscopy in the ν(C-H) region confirms that the hydrophobic C-terminal of Aβ(1-40) inserts itself into the hydrophobic part of the SPBs. The Raman data indicate that α-helix and β-sheet structures of Aβ(1-40) increase and coexist over longer time frames. Based on these results, a model was proposed to describe the mechanism of the conformational changes and the aggregation of Aβ(1-40) that are mediated by ganglioside-GM1-containing SPBs.

Direct Observation of Amyloid β Behavior at Phospholipid Membrane Constructed on Gold Nanoparticles

“…Based on the membrane-enabled adoption, A β tends to aggregate into β -sheet [17–19]. Additionally, some part of A β will insert in membrane as α -helix or random coil with hydrophobic interaction [20]. In this study, the anionic PL accelerated the A β fibrillation, which is consistent with previous studies.…”

“…Comparing Raman spectra of Au@PL and Au@PL with addition of A β shown in Figures 4(a) and 4(b), Raman signals at 1031 cm −1 , 1374 cm −1 , 2905 cm −1 and 2966 cm −1 appeared in the presence of A β before incubation. Based on studies of Hu et al and Raman spectra of pure A β (Figure 4(c)), these four peaks are attributed to A β [20]. It is suggested that A β probably appeared near hot spot of nanoparticles so its Raman was enhanced.…”

Amyloid-β fibrils assembled on ganglioside-enriched membranes contain both parallel β-sheets and turns

“…7) in which monomeric A␤ forms an initial layer not only on GM1-enriched nanoclusters but also on sphingomyelin/cholesterol area (step a) (29,30). NMR (36) and Raman spectroscopic studies (37) indicated that A␤ at ganglioside nanoclusters then forms helices (step b, GA␤ formation); however, a prominent helical peak at 1650 -1657 cm Ϫ1 was not observed (see Fig. 5A).…”

β‐Amyloid aggregation and heterogeneous nucleation

“…And in yet a different study, conducted using lower GM 1 mol%, one group reported that SM triggers oligomerization of Aβ40, while GM 1 prevents it. Various other studies using NMR, CD and FTIR, and Raman spectroscopy also have suggested an α‐helix to β‐sheet transition, though comparison across studies is not always possible. Such studies underscore the complexity of these interactions, which still awaits clarification …”