%0 Journal Article
%A Henry, Sarah
%A Vignaud, Hélène
%A Bobo, Claude
%A Decossas, Marion
%A Lambert, Oliver
%A Harte, Etienne
%A Alves, Isabel
D.
%A Cullin, Christophe
%A Lecomte, Sophie
%D 2015
%T Interaction of Aβ1–42 Amyloids
with Lipids Promotes “Off-Pathway” Oligomerization and
Membrane Damage
%U https://acs.figshare.com/articles/journal_contribution/Interaction_of_A_sub_1_42_sub_Amyloids_with_Lipids_Promotes_Off_Pathway_Oligomerization_and_Membrane_Damage/2188684
%R 10.1021/bm501837w.s001
%2 https://ndownloader.figshare.com/files/3822850
%K WT
%K Membrane DamageThe toxicity
%K perturbs liposome organization
%K PG membrane fragmentation
%K membrane disruption
%K oG 37C
%K interaction
%K peptides destabilized liposomes
%K fiber formation
%K L 34T mG 37C
%K plasmon waveguide resonance
%K Many studies link
%X The
toxicity of amyloids, as Aβ1–42 involved
in Alzheimer disease, is a subject under intense scrutiny. Many studies
link their toxicity to the existence of various intermediate structures
prior to fiber formation and/or their specific interaction with membranes.
In this study we focused on the interaction between membrane models
and Aβ1–42 peptides and variants (L34T, mG37C)
produced in E. coli and purified in
monomeric form. We evaluated the interaction of a toxic stable oligomeric
form (oG37C) with membranes as comparison. Using various biophysical
techniques as fluorescence and plasmon waveguide resonance, we clearly
established that the oG37C interacts strongly with membranes leading
to its disruption. All the studied peptides destabilized liposomes
and accumulated slowly on the membrane (rate constant 0.02 min–1). Only the oG37C exhibited a particular pattern of
interaction, comprising two steps: the initial binding followed by
membrane reorganization. Cryo-TEM was used to visualize the peptide
effect on liposome morphologies. Both oG37C and mG37C lead to PG membrane
fragmentation. The PG membrane promotes peptide oligomerization, implicated
in membrane disruption. WT (Aβ1–42) also perturbs
liposome organization with membrane deformation rather than disruption.
For all the peptides studied, their interaction with the membranes
changes their fibrillization process, with less fibers and more small
aggregates being formed. These studies allowed to establish, a correlation
between toxicity, fiber formation, and membrane disruption.
%I ACS Publications