Abstract
The conformational behavior of the amyloid-β42 (Aβ42) peptide is strongly influenced by the physical state of its surrounding lipid environment. The effect of temperature on the Aβ42 structure within dipalmitoylphosphatidylcholine (DPPC) bilayers was investigated using circular dichroism (CD), Raman spectroscopy, and molecular dynamics (MD) simulations. The study examined two thermal phases: room temperature (RT =∼ (25±2)◦C), corresponding to the gel phase of DPPC, and (48±2)◦C, representing the fluid phase above the lipid transition temperature. The CD spectroscopy measurements indicated a clear temperature-dependent structural transition of the peptide. At RT, Aβ42 exhibited a conformation enriched in β structures, while at (48±2)◦C, the spectra revealed a notable increase in α-helical content, reflecting enhanced backbone organization under fluid-phase conditions. Raman spectral analysis supported this trend by demonstrating an increased contribution of α-helical components accompanied by a reduction in β-strand features upon heating. Minor variations in lipid vibrational markers further suggested greater acyl-chain flexibility and bilayer fluidity in the high-temperature state. Furthermore, MD simulations revealed enhanced α-helical content and deeper peptide insertion within the disordered bilayer compared with the ordered gel phase. The findings from experimental and computational investigations demonstrate that membrane fluidization above the DPPC phase transition favors α-helical stabilization of Aβ42, emphasizing temperature as a key parameter governing peptide–lipid conformational equilibria. The results obtained provide a fundamental framework for understanding how thermal conditions modulate amyloid-membrane interactions, which is essential for elucidating the early molecular events associated with amyloid-related pathologies.