Single Molecule Dynamic Transduction by Carbon Nanotube Circuits

Nanoscale electronic devices like field-effect transistors (FETs) have long promised to provide sensitive, label-free detection of biomolecules. In particular, single-walled carbon nanotubes (SWNTs) have the requisite sensitivity to detect single molecule events, and have sufficient bandwidth to directly monitor single molecule dynamics in real time. Recent measurements have demonstrated this premise by monitoring the dynamic, single-molecule processivity of three different enzymes: lysozyme, protein kinase A, and the Klenow Fragment of polymerase I. Initial successes in each case indicated the generality and attractiveness of SWNT FETs as a new tool to complement other single molecule techniques. However, further generalization of the SWNT FET technique demands reliable design rules that can predict the success and applicability of these devices. Here, we address this need by focusing on the transduction mechanisms that link enzyme processivity to electrical signal generation in a SWNT FET. Using ten different lysozyme variants synthesized by mutagenesis, we systematically dissect the enzyme-SWNT interaction in order to understand this transduction. The data prove that mechanical displacements of charged functionalities near the SWNT attachment site are the primary sources of transduction, and that the resulting devices are sensitive enough to track the motions of just one charged amino acid. The purposeful incorporation of a charged group at a particular location allows the device to be designed to have sensitivity to particular chemical activities or allosterically-driven mechanical motions. The findings provide rules for the creation of similarly effective nanocircuits using a wide range of enzymes or proteins.