Molecular Insights for Alzheimer’s Disease: An Unexplored Storyline on the Nanoscale Impact of Nascent Aβ 1–42 toward the Lipid Membrane
Abstract
Deciphering the mechanism of Alzheimer’s disease is a key element for designing an efficient therapeutic strategy. Molecular dynamics (MD) calculations, atomic force microscopy and infrared spectroscopy were combined to investigate β-amyloid (Aβ1-42) peptide interactions with supported lipid bilayers (SLBs). The MD simulations showed that nascent Aβ1-42 monomers remain anchored within a model phospholipid bilayer’s hydrophobic core, which suggests their stability in their native environment. We tested this prediction experimentally, by studying the behavior of Aβ1-42 monomers and oligomers when interacting with SLBs. When Aβ1 42 monomers and oligomers were self-assembled with lipid bilayer and deposited as SLB, they remain within the bilayers. Their presence in the bilayers induces destabilization of the model membranes. No specific interactions between Aβ1 42 and the SLBs were detected when SLBs free of Aβ1-42 were exposed to Aβ1-42. This study suggests that Aβ can remain in the membrane after cleavage by the γ-secretase, and cause severe damage in the membrane.