Electrochemical assessment of dielectric damage to phospholipid bilayers by amyloid β-Oligomers.

Amyloid beta (Aβ) oligomers produced in vitro with and without the oligomerization inhibitor hexafluoroisopropanol (HFIP) were studied and compared as agents inflicting damage to the phospholipid bilayers. Tethered lipid membranes (tBLMs) of different compositions were used as model membranes. Dielectric damage of tBLMs by Aβ oligomers was monitored by the electrochemical impedance spectroscopy (EIS). Membranes containing sphingomyelin exhibited the highest susceptibility to Aβ oligomers when assembled in the absence of an inhibitor. The activation barrier of ion translocation through the Aβ oligomer entities in tBLMs was lowest in sphingomyelin membranes (<15 kJ/mol). This is consistent with the formation of water-filled, highly conductive (>50 pS) nanopores in tBLMs by Aβ oligomers assembled without HFIP. Conversely, HFIP-generated Aβ oligomers exhibited conductance with high activation energies (>38 kJ/mol), suggesting the formation of assemblies with relatively narrow ion pores and the effective conductance in the range < 15 pS. Finally, the EIS data analysis revealed differences in the lateral distribution of Aβ oligomers in tBLMs. The inhibitor-free Aβ oligomers populate the tBLM surface in a random manner, whereas the HFIP-generated Aβ oligomers tend to cluster forming surface areas with markedly different densities of Aβ defects.