Abstract
Amyloid fibril disaggregation has been observed recently upon
incubation with lipid vesicles, challenging the view of fibrils as end states of the
aggregation process in vivo. Here, we follow fibril disaggregation in the presence
of lipid vesicles by means of molecular dynamics simulations, using simplified
models of peptides and lipids. The simulation results show that disaggregation is
driven by an entropy increase and yields soluble protofibrillar intermediates.
These intermediates are different fromthemetastable oligomers observed during
fibril formation, and their stability depends on the morphology of the parent
fibril.
Friedman, R