Abstract
Aggregation of misfolded Amyloid-beta (Abeta) peptides into highly structured oligomeric forms, particularly on lipid membranes is suspected as the primary event in Alzheimer's pathogenesis. Coarse grained molecular dynamics (CG-MD) simulations can provide detailed structural and dynamical characterization of membrane-induced amyloid-beta oligomers. To investigate the differential effects of anionic and zwitterionic lipids on aggregation of Abeta central hydrophobic core (residues 16-22: K-L-V-F-F-A-E) in presence of lipid bilayers, we employed CG-MD simulations of model lipid bilayers with solvated monomeric peptides. Similar to experimental observations, the fraction of ordered beta sheet rich fibrils is higher on anionic - 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS) bilayer as compared to zwitterionic - 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer. On the other hand, the total rate of aggregation (both ordered and disordered), is higher for POPC. We also evaluate other lipid induced morphological features of peptide-aggregates and provide mechanistic explanations derived from lipid-peptide interaction for our observations. This work highlights the importance of lipid headgroup in introducing kinetic variations and structural diversity on Amyloid-beta 16-22 peptide aggregation.
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