bc200077s_si_001.pdf (7.47 MB)
Template-Assisted Lateral Growth of Amyloid-β42 Fibrils Studied by Differential Labeling with Gold Nanoparticles
journal contribution
posted on 2016-02-22, 08:19 authored by Muriel Arimon, Fausto Sanz, Ernest Giralt, Natàlia CarullaAmyloid-β protein (Aβ) aggregation into amyloid
fibrils
is central to the origin and development of Alzheimer’s disease
(AD), yet this highly complex process is poorly understood at the
molecular level. Extensive studies have shown that Aβ fibril
growth occurs through fibril elongation, whereby soluble molecules
add to the fibril ends. Nevertheless, fibril morphology strongly depends
on aggregation conditions. For example, at high ionic strength, Aβ
fibrils laterally associate into bundles. To further study the mechanisms
leading to fibril growth, we developed a single-fibril growth assay
based on differential labeling of two Aβ42 variants with gold
nanoparticles. We used this assay to study Aβ42 fibril growth
under different conditions and observed that bundle formation is preceded
by lateral interaction of soluble Aβ42 molecules with pre-existing
fibrils. Based on this data, we propose template-assisted lateral
fibril growth as an additional mechanism to elongation for Aβ42
fibril growth.