Arrangement of lipid vesicles and bicelle-like structures formed in the presence of Aβ(25-35) peptide

Abstract

Our complementary experimental data and molecular dynamics (MD) simulations results reveal the structure of previously observed lipid bicelle-like structures (BLSs) formed in the presence of amyloid-beta peptide Aβ(25-35) below the main phase transition temperature (T_m) of saturated phosphatidylcholine lipids and small unilamellar vesicles (SUVs) above this temperature. First, we show by using solid-state ³¹P nuclear magnetic resonance (NMR) spectroscopy that our BLSs being in the lipid gel phase demonstrate magnetic alignment along the magnetic field of NMR spectrometer and undergo a transition to SUVs in the lipid fluid phase when heated through the T_m. Secondly, thanks to the BLS alignment we present their lipid structure. Lipids are found located not only in the flat bilayered part but also around its perimeter, which is corroborated by the results of coarse-grained (CG) MD simulations. Finally, peptides appear to mix randomly with lipids in SUVs while assuming predominantly unordered secondary structures revealed by circular dichroism (CD), Raman spectroscopy, and all-atom MD simulations. Importantly, the former is changing little when the system undergoes morphological transitions between BLSs and SUVs. Our structural results then offer a platform for studying and understanding mechanisms of morphological transformations caused by the disruptive effect of amyloid-beta peptides on the lipid bilayer.

Keywords: Amyloid-β peptide; Bicelle-like structure; Circular dichroism; Coarse-grained molecular dynamics; Nuclear magnetic resonance; Raman spectroscopy.