Amyloid‑β Peptide Triggers Membrane Remodeling in Supported Lipid Bilayers Depending on Their Hydrophobic Thickness

Amyloid-β
(Aβ) peptide has been implicated in Alzheimer’s
disease, which is a leading cause of death worldwide. The interaction
of Aβ peptides with the lipid bilayers of neuronal cells is
a critical step in disease pathogenesis. Recent evidence indicates
that lipid bilayer thickness influences Aβ membrane-associated
aggregation, while understanding how Aβ interacts with lipid
bilayers remains elusive. To address this question, we employed supported
lipid bilayer (SLB) platforms composed of different-length phosphatidylcholine
(PC) lipids (C12:0 DLPC, C18:1 DOPC, C18:1-C16:0 POPC), and characterized
the resulting interactions with soluble Aβ monomers. Quartz
crystal microbalance-dissipation (QCM-D) experiments identified concentration-dependent
Aβ peptide adsorption onto all tested SLBs, which was corroborated
by fluorescence recovery after photobleaching (FRAP) experiments indicating
that higher Aβ concentrations led to decreased membrane fluidity.
These commonalities pointed to strong Aβ peptide–membrane
interactions in all cases. Notably, time-lapsed fluorescence microscopy
revealed major differences in Aβ-induced membrane morphological
responses depending on SLB hydrophobic thickness. For thicker DOPC
and POPC SLBs, membrane remodeling involved the formation of elongated
tubule and globular structures as a passive means to regulate membrane
stress depending on Aβ concentration. In marked contrast, thin
DLPC SLBs were not able to accommodate extensive membrane remodeling.
Taken together, our findings reveal that membrane thickness influences
the membrane morphological response triggered upon Aβ adsorption.