Single-molecule protein unfolding in solid state nanopores

David S. Talaga, Jiali Li

Research output: Contribution to journalArticlepeer-review

353 Scopus citations


We use single silicon nitride nanopores to study folded, partially folded, and unfolded single proteins by measuring their excluded volumes. The DNA-calibrated translocation signals of β-lactoglobulin and histidine-containing phosphocarrier protein match quantitatively with that predicted by a simple sum of the partial volumes of the amino acids in the polypeptide segment inside the pore when translocation stalls due to the primary charge sequence. Our analysis suggests that the majority of the protein molecules were linear or looped during translocation and that the electrical forces present under physiologically relevant potentials can unfold proteins. Our results show that the nanopore translocation signals are sensitive enough to distinguish the folding state of a protein and distinguish between proteins based on the excluded volume of a local segment of the polypeptide chain that transiently stalls in the nanopore due to the primary sequence of charges.

Original languageEnglish
Pages (from-to)9287-9297
Number of pages11
JournalJournal of the American Chemical Society
Issue number26
StatePublished - 8 Jul 2009


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