Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Monday Speaker Abstracts

Single Molecule Fluorescence Clarifies the Role of Monosialoganglioside GM1 and Sphingomyelin in the In-Membrane Oligomerization of β-Amyloid Martin Hof , Mariana Amaro, Radek Sachl, Gokcan Aydogan. J. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Prague, Czech Republic. Oligomers of the β-amyloid (Aβ) peptide are thought to be implicated in Alzheimer’s disease. The plasma membrane of neurons may mediate the oligomerization of Aβ present in brain. Using the single-molecule sensitivity of fluorescence, we address the oligomerization of Aβ monomers on lipid bilayers containing essential components of the neuronal plasma membrane. We find that Sphingomyelin triggers the oligomerization of Aβ and that physiological levels of GM1, organized in nanodomains, do not seed oligomerization. Moreover, GM1 prevents oligomerization of Aβ counteracting the effect of Sphingomyelin. Our results establish a preventive role of GM1 in the oligomerization of Aβ suggesting that decreasing levels of GM1 in brain, e.g. due to aging, could lead to reduced protection from the oligomerization of Aβ and contribute to Alzheimer's onset. In addition to the new insights into the molecular mechanism(s) that may be involved in Alzheimer’s disease, it should be pointed out that this work contains a further important novel finding. We uncovered the existence of nanoscopic heterogeneities (radius 8-26 nm) in microscopically homogenous membranes. This was achieved by a combination of Monte Carlo Simulations, FLIM-FRET and FCS techniques using recently developed fluorescent ganglioside analogues. Such nano-heterogeneities are unresolvable by standard and super-resolution microscopy.

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