Controlling the translocation of proteins through nanopores with bioinspired fluid walls

Synthetic nanopores have been used to study individual biomolecules in high thoroughput but their performance as sensors does not match biological ion channels. Controlling the translocation times of single-molecule analytes and their non-specific interaction with pore walls remain a challenge. Inspired by the olfactory sensilla of the insect antenna, here we show that coating nanopores with fluid bilayer lipids allows the pore diameters to be fine-tuned in sub-nanometre increments. Incorporation of mobile ligands in the lipid conferred specificity and slowed down the translocation of targeted proteins sufficiently to time-resolve translocation events of individual proteins. The lipid coatings also prevented pores from clogging, eliminated non-specific binding and enabled the translocation of amyloid-beta (Aβ) oligomers and fibrils. Through combined analysis of translocation time, volume, charge, shape and ligand affinity, different proteins were identified.