Amyloid-beta Peptide Triggers Membrane Remodeling in Supported Lipid Bilayers Depending on Their Hydrophobic Thickness
Year: 2018
Journal: Langmuir, Volume 34, AUG 14, page 9548–9560
Authors: Meker, Sigalit; Chin, Hokyun; Sut, Tun Naw; Cho, Nam-Joon
Amyloid-beta (A beta) peptide has been implicated in Alzheimer's disease, which is a leading cause of death worldwide. The interaction of A beta peptides with the lipid bilayers of neuronal cells is a critical step in disease pathogenesis. Recent evidence indicates that lipid bilayer thickness influences A beta membrane-associated aggregation, while understanding how A beta 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 A beta monomers. Quartz crystal microbalance-dissipation (QCM-D) experiments identified concentration-dependent A beta peptide adsorption onto all tested SLBs, which was corroborated by fluorescence recovery after photobleaching (FRAP) experiments indicating that higher A beta concentrations led to decreased membrane fluidity. These commonalities pointed to strong A beta peptide membrane interactions in all cases. Notably, time-lapsed fluorescence microscopy revealed major differences in A beta 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 A beta 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 A beta adsorption.
