A confined nanopipette for time-resolved protein-lipid interactions.

Abstract

The microtubule-binding protein has been reported to contribute to the pathology of neurodegenerative diseases such as Alzheimer's disease. Although it is widely known that tau functions in neuronal and glial cells with a highly diversity of membrane morphology and tau protein could induce the morphology change of vesicles via binding, it is still unclear whether the membrane morphology plays a role in tau pathology. Little is known about dynamic interaction between tau and lipid and the precise mechanism by which tau induces neuron damage through binding to membrane. Thus, investigating the time-resolved tau-lipid interactions, especially in complex membrane environment, is of vital significance. Here, we developed a confined nanopipette method to construct a complex lipid environment with diverse membrane morphologies. The tau-lipid interactions were effectively confined in the nanopipette electrochemical sensing region, where the time-series current recording reveals the dynamic binding profiles. Two different tau-lipid interaction models were proposed to contribute to the observed current oscillation, that either the dynamic tau conformations or membrane morphology change with the interactions. Finite element modeling was employed to provide an improved understanding of the interaction-induced current oscillation. Our results also show great promise for other model membrane protein, offering a time-resolved prospect for these fundamental biological processes.