Molecular chirality mediated amyloid formation on phospholipid surfaces
Xue Wang, Cunli Wang, Huiying Chu, Haijuan Qin, Dongdong Wang, Feifei Xu, Xuanjun Ai, Chunshan Quan, Guohui Li, Guangyan Qing
Abstract
-glycero-3-phosphoethanolamine (l-/d-Asp-DPPE) is synthesized to construct chiral phospholipid bilayers. We discover that the l-Asp-DPPE liposomes slightly inhibit the Aβ(1-40) nucleation process but cannot affect the oligomer elongation process. By contrast, the d-Asp-DPPE liposomes strongly inhibit both nucleation and elongation of the peptide. Notably, l- and d-Asp-DPPE liposomes not only have good biocompatibility but can also rescue Aβ(1-40)-aggregation induced cytotoxicity with significant chiral discrimination, in which the cell viability is higher in the presence of d-Asp-DPPE liposomes. Mechanism analysis and molecular dynamics simulation clearly demonstrate that differential electrostatic interactions of Lys16 in Aβ(1-40) with l- or d-Asp on the phospholipid contribute to the remarkable chiral discrimination. This study provides a deeper understanding of the crucial amyloidosis process from the perspective of the chiral interface and reveals that the convergence of d-amino acids with the liposomes might be a feasible route for AD prevention.