Single-molecule Mapping of Amyloid-β Oligomer Insertion intoLipid Bilayers

Abstract

The interaction of disease-causing amyloid oligomers with lipid membranes is implicated in their toxicity. However, understanding the membrane interaction of different oligomers, and each constituent monomer in a given oligomer, has remained a challenge. Here we employed a recently developed single-molecule technique, called QSLIP, which can simultaneously determine the stoichiometry and membrane location of individual fluorescent labels on oligomeric membrane proteins. Using QSLIP, we measured the membrane insertion of small amyloid-beta (A{beta}) oligomers of three different isoforms at the single-molecule level, and found that their toxicity is correlated with the depth of penetration of their amino-terminal into the bilayer. Such single-molecule maps provide a detailed assay for measuring the effect of any drug candidate on oligomer-membrane interactions.