Toward Sensing Protein Interactions and Dynamics via 1/ <i>f</i> Noise in Graphene Field-Effect Transistors

Graphene field-effect transistors (GFETs) functionalized with lipid monolayers provide a sensitive platform for probing membrane protein dynamics. Here, we analyze the effect of peripheral membrane proteins on this assay. We focused on the prenylated Rab7 GTPase Ypt7 and its interacting HOPS tethering complex using liquid-gated GFETs combined with low-frequency noise spectroscopy. Current–voltage (I–[Formula: see text] transfer measurements reveal no or only very small changes upon binding of Ypt7 and after addition of HOPS. In contrast, noise analysis reveals pronounced flicker (1/[Formula: see text] noise level growth after Ypt7 binding, most likely due to conformational dynamics of Ypt7. Recruitment of the HOPS complex by Ypt7 to membranes inhibits these fluctuations, suggesting structural stabilization of Ypt7 via HOPS binding. Our findings demonstrate that noise spectroscopy allows for enhancing the sensitivity of GFET-based biosensing, offering insights into protein–membrane and protein–protein interactions beyond traditional electronic readouts.