25 / 120
Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Monday Speaker Abstracts
20
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.