Electrostatic peptide-lipid interactions of amyloid-beta peptide and pentalysine with membrane surfaces monitored by P-31 MAS NMR

High-resolution P-31 magic angle spinning (MAS) NMR spectroscopy is present ed as a direct and non-perturbing method for measuring changes in surface c harge density occurring in mixed phospholipid membranes upon binding of cha rged surface-active peptides. P-31 MAS NMR was used to investigate mixed li pid membranes of neutral phosphatidylcholine and negatively charged phospha tidylglycerol where the molar fraction of the charged lipid was varied from 0 to 1. The chemical shifts of the individual membrane lipids showed a sim ple variation in response to changes in the fraction of the negatively char ged component phosphatidylglycerol. Addition of the positively charged amyl oid-beta (1-40) peptide, a key substance in Alzheimer's disease, resulted i n changes in the isotropic chemical shifts of the membrane lipid phosphates in a way consistent with reduction in the negative surface charge of the m ixed lipid bilayers. Binding of different amounts of the positively charged peptide pentalysine to L-alpha -dioleoylphosphatidylcholine/L-alpha -diole oylphosphatidylglycerol (DOPC/DOPG) vesicles (2:1 molar ratio) also showed a systematic variation of both chemical shift values. These changes were de scribed by a simple two-site model and indicate purely electrostatic bindin g of pentalysine.