Lipid-Modified Graphene-Transistor Biosensor for Monitoring Amyloid-β Aggregation

A graphene field-effect transistor (G-FET) with the spacious planar graphene surface can provide a large-area interface with cell membranes to serve as a platform for the study of cell membrane-related protein interactions. In this study, a G-FET device paved with a supported lipid bilayer (referred to as SLB/G-FET) was first used to monitor the catalytic hydrolysis of the SLB by phospholipase D. With excellent detection sensitivity, this G-FET was also modified with a ganglioside G_M1-enriched SLB (G_M1-SLB/G-FET) to detect cholera toxin B. Finally, the GM1-SLB/G-FET was employed to monitor amyloid-beta 40 (Aβ40) aggregation. In the early nucleation stage of Aβ40 aggregation, while no fluorescence was detectable with traditional thioflavin T (ThT) assay, the prominent electrical signals probed by G_M1-SLB/G-FET demonstrate that the G-FET detection is more sensitive than the ThT assay. The comprehensive kinetic information during the Aβ40 aggregation could be collected with a G_M1-SLB/G-FET, especially covering the kinetics involved in the early stage of Aβ40 aggregation. These experimental results suggest that SLB/G-FETs hold great potential as a powerful biomimetic sensor for versatile investigations of membrane-related protein functions and interaction kinetics.