Multidimensional Investigations of Single Molecule Unfolding of Bovine Serum Albumin Using Plasmonic Nanopores.

Direct detection of proteins, especially their conformation and configuration information, at the single molecule level, is challenging in various biotechnological fields. Plasmonic nanopores have raised attention as multidimensional biosensors with single molecule (SM) sensitivity. Here, we employ a gold plasmonic nanopore to monitor the unfolding of SM bovine serum albumin (BSA). The gradual collapse of the BSA structure induced by high bias voltages is demonstrated through an increase in the fraction current blockade. Surface-enhanced Raman scattering (SERS) spectra provide structural evidence for protein unfolding, while the optical force is verified as an additional factor contributing to BSA deformation. The effect of the optical force on the dwell time of BSA in a nanopore is also investigated. The present study reveals that plasmonic nanopores offer multidimensional observations on the structure and conformation of SM proteins, which will drive further innovations in protein detection and analysis.