Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Soluble Amyloid [Beta] Oligomers Affect Dielectric Properties by Membrane Incorporation and Domain Formation: Implications for Cell Toxicity



G Valinius, K F. Heinrich, R Budvytye, David J. Vanderah, Y Sokolov, J Hall, M Losche


Water-soluble prefibrillar amyloid b (Ab1 42) oligomers affect model bilayers by greatly reducing the membrane barrier to ion transport, as previously reported for Ab in many papers. However, important signatures of the molecular transport mechanism are distinctly different from those for ion transfer facilitated by the bacterial membrane pore, a-hemolysin (aHL). Ab oligomers at mM peptide concentrations inserted readily into lipid membranes, affecting both leaflets of the bilayer equally. This was shown with neutron reflectometry of substrate-supported tethered bilayers disjoined from the inorganic substrates by nanometer-thick water/oligo(ethylene oxide) cushions. Upon rinsing of the membrane, Ab oligomers were quantitatively removed from the bilayer. By measuring the capacitance of the peptide-free membranes and their geometrical thicknesses, the dielectric constants were determined to be e = 2.8 and 2.2 in the aliphatic cores of DOPC and DPhyPC bilayers, respectively. Quantitative evaluations of electrochemical impedance spectra and neutron reflection both indicated that Ab oligomers affect membranes by inducing lateral heterogeneity in the lipid bilayers. However, an increase of the water content was not detected in the bilayers by neutron reflection. Moreover, the activation energy for amyloid-induced ion transport across the membrane is at least by a factor 3x higher than that measured for membranes reconstituted with aHL pores, Ea = 36.8 kJ/mol vs. 9.9 kJ/mol, indicating that the molecular mechanisms underlying both transport processes are fundamentally different. The amyloid-induced ion conductances across tethered and across free-standing membranes are quantitatively similar and show a substantial dependence on membrane composition. A model in which Ab oligomers insert into the hydrophobic core of the membrane where they lead to a substantial local increase in e and a concomitant local breakdown of the membrane barrier described all experimental data quantitatively.
Journal of General Physiology


Valinius, G. , Heinrich, K. , Budvytye, R. , Vanderah, D. , Sokolov, Y. , Hall, J. and Losche, M. (2021), Soluble Amyloid [Beta] Oligomers Affect Dielectric Properties by Membrane Incorporation and Domain Formation: Implications for Cell Toxicity, Journal of General Physiology (Accessed April 24, 2024)
Created October 12, 2021