A synapse-mimicking nanopipette method was developed to electrochemically monitor single vesicle dynamics induced by lipid-tau interactions. To mimic the lipid environment in synapses, model vesicles and a modified lipid layer were confined within a nanopipette, as reported by Ru-Jia Yu, Yi-Tao Long et al. in their Communication (e202406677). Characteristic ionic current oscillations were recorded and could be used to evaluate the binding affinity of tau protein, indicating that phosphorylated tau inhibits vesicle dynamics through strong interactions with synaptic vesicles.