부산대학교 도서관

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 Aβ1–42monomers 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 Aβ1–42monomers and oligomers when interacting with SLBs. When Aβ1–42monomers and oligomers were self-assembled with a lipid bilayer and deposited as an SLB, they remain within the bilayers. Their presence in the bilayers induces destabilization of the model membranes. No specific interactions between Aβ1–42and the SLBs were detected when SLBs free of Aβ1–42were exposed to Aβ1–42. This study suggests that Aβ can remain in the membrane after cleavage by γ-secretase and cause severe damage to the membrane.