Dual-diameter α-helical nanopores from a single peptide enable ultrasensitive biomarker profiling
Researchers created pPorA, a single 40-amino-acid peptide that self-assembles into octameric α-helical nanopores with two conductance states (S ≈ 2.4 nS and L ≈ 3.5 nS) in lipid membranes. By incorporating unnatural amino acids, they tune pore diameter to achieve size-, charge-, and stereoselective sensing of diverse biomarkers, from sugars and enantiomeric peptides to intrinsically disordered disease proteins. The large pores detect multiple α-synuclein variants with nanomolar affinity and enable charge-resolved discrimination of species, while the small pores sense small peptides like humanin and SOD1. The study reveals time-dependent α-syn aggregation pathways inside the pores and confirms structural insights with MD simulations, presenting a programmable nanopore platform for ultrasensitive biomarker profiling and potential drug screening.
