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

Abstract

Amyloid beta (Aβ1-42) 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 Aβ1-42 oligomers was monitored by the electrochemical impedance spectroscopy (EIS). Membranes containing sphingomyelin exhibited the highest susceptibility to Aβ1-42 oligomers when assembled in the absence of an inhibitor. The activation barrier of ion translocation through the Aβ1-42 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 Aβ1-42 oligomers assembled without HFIP. Conversely, HFIP-generated Aβ1- 42 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 Aβ1-42 oligomers in tBLMs. The inhibitor-free Aβ1-42 oligomers populate the tBLM surface in a random manner, whereas the HFIP-generated Aβ1-42 oligomers tend to cluster forming surface areas with markedly different densities of Aβ1-42 defects.