Simply put, nanopores form very small holes through impermeable barriers. These passageways enable ions and molecules to move from one side of the barrier to the other in a way that creates detectable signatures. These signatures can be used for chemical sensing. Several different kinds of ion channels can be engineered to create nanopore sensors. By recombinantly synthesizing mutant protein structures to add a desired feature at the mutation site (e.g., excess charge, structural bulk, flexible polymer strands, or a binding moiety) wild-type ion channels can be transformed into molecular devices for specific sensing applications.
More specifically, our group has been working to create a number of nanopore cap modifications to the alpha-hemolysin (αHL) ion channel. Once these novel materials are created, measurement specialists then characterize the resulting relationship between the protein structure and function using a variety of techniques (e.g., single-channel electrophysiology, single-molecule fluorescence, lysis assays). Lastly, results from the synthetic and characterization efforts are combined with computer simulations that model kinetic motion and the impact of electric fields that span nanopore-forming biomolecules. As understanding of the underlying signal-production mechanisms grows, these models have potential to assist in the design and synthesis of new nanopore structures.