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 from the metastable oligomers observed during fibril formation, and their stability depends on the morphology of the parent fibril.
BT - The Journal of Physical Chemistry Letters C1 - 0124 DA - Jan 21 2010 DO - 10.1021/jz900318t IS - 2 J2 - J. Phys. Chem. Lett. LA - eng M3 - Research Article N2 -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 from the metastable oligomers observed during fibril formation, and their stability depends on the morphology of the parent fibril.
PY - 2010 SP - 471 EP - 474 T2 - The Journal of Physical Chemistry Letters TI - Soluble protofibrils as metastable intermediates in simulations of amyloid fibril degradation induced by lipid vesicles UR - http://dx.doi.org/10.1021/jz900318t VL - 1 ER -