Structure of the Alzheimer β-amyloid peptide (25-35) and its interaction with negatively charged phospholipid vesicles

The secondary structure of amyloid beta AP(25-35) peptide was studied in pure form and in the presence of different phospholipid vesicles, by using Fourier transform infrared spectroscopy (FT-IR). Purl peptide aggregated with time, forming fibrils with beta-structure. Phospholipid vesicles formed by negatively charged phospholipids such as 1,2-dimyristoyl-sn-glycerol-3-phospho-L-serine (Myr(2)PtdSer), 1,2-dimyristoyl-sn-glycerol-3-phospho-rac-1-glycerol (Myr(2)PtdGro) and 1,2-dimyristoyl-sn-glycerol 3-phosphate (Myr(2)PtdH), greatly accelerated the aggregation of the peptide. However, the presence of vesicles formed by the zwitterionic phospholipid, 1,2-dimyristoyl-sn-glycerol-3-phosphocholine (Myr(2)PtdCho), slowed down the aggregation process. Differential scanning calorimetry (DSC) measurements showed that the effect of PAP(25-35) on the gel to crystal liquid phase transition was small at neutral pH for negatively charged phospholipids and practically nil for Myr(2)PtdCho. In the case of Myr(2)PtdSer the effect was also zero at pH 9 but the effect was large at pH 3. The effect on Myr(2)PtdH was not, however, very dependent on pH. These results were fully confirmed by the observation through FT-IR of the change with temperature of the CH2 antisymmetric stretching vibration. The case of Myr(2)PtdGro was special as this phospholipid presents polymorphism giving solid quasicrystalline phases when it is not sufficiently hydrated, and it is remarkable that PAP(25-35) was able to induce the formation of crystalline phases in samples prepared through a method which ensure a good hydration of phospholipid. These results show that the interaction of amyloid PAP(25-35) peptide with phospholipids is based on electrostatic interactions, that these interactions favour the aggregation of the peptides, and that the presence of the aggregates may disturb the lipid-water interphase of the membrane.