The objective of our research study is to address contemporary scientific challenges, with a particular focus on the intricate mechanisms underlying neurodegenerative disorders, with a specific interest in Alzheimer’s disease (AD). The focus of our research is the pivotal interplay between peptides and lipids, where minor disruptions in these interactions is believed to be linked to the pathogenesis of several diseases. Notably, the misfolding and aggregation of peptides within the membrane are postulated to be significant contributors to the onset and progression of Alzheimer’s disease. Therefore, understanding the interactions between Aẞ-42 and cellular structures is crucial for the early detection and prevention of Alzheimer’s disease.

In this study, a comprehensive Raman spectroscopic analysis was conducted to investigate the conformational dynamics of Aẞ-42 in aqueous environments and within lipid membrane mimetics, such as liposomes and lipodiscs. Our findings indicate that the a-helix secondary structure predominates in liposomes. Conversely, in lipodiscs, Aẞ-42 adopts a ẞ-turn/random coil conformation, a transition that was not anticipated. The results of the Raman study have shown that Aẞ-42 peptides presented in liposomes maintain their native form, unlike lipodiscs. The copolymer affects the lipid bilayer, altering its conformation and preventing the peptide from maintaining its original structure.

To further substantiate the experimental observations, we employed molecular dynamics (MD) and density functional theory (DFT) simulations, which demonstrated strong concordance with the Raman spectroscopy results. This integrative approach enhances our understanding of AB-42 conformational behavior in different lipid environments, offering valuable insights into the molecular underpinnings of Alzheimer’s disease.