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 signtures can be used for chemical sensing. Our group focuses on developing protein-based nanopores that act as ion channels in cell membranes. By recombinantly synthesizing mutant protein structures, followed by a second step of chemical modification to add a desired feature (i.e., charge, structural bulk, polymer flexibility, or specific binding capacity) relatively unuseful 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.