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Developing Single-Molecule Technique with Microsecond Resolution

  • Author(s): Akhterov, Maxim V.
  • Advisor(s): Collins, Philip G.
  • et al.
Abstract

Molecular machines like proteins are responsible for many regulatory and catalytic functions. Specifically, molecular motions of proteins and their flexibility determine conformational states required for enzyme catalysis, signal transduction, and protein-protein interactions. However, the mechanisms for protein transitions between conformational states are often poorly understood, especially in the milli- to microsecond ranges where conventional optical techniques and computational modeling are most limited. This work describes development of an electronic single-molecule technique for monitoring microsecond motions of biological molecules. Dynamic changes of conductance through a transistor made of a single-walled carbon nanotube (SWNT-FET) report conformational changes of a protein molecule tethered to the SWNT sidewall. In principle, the high operating speed of SWNT-FETs could allow this technique to resolve molecular events with nanosecond resolution. This project focused on improving the technique to a 200 kHz effective bandwidth in order to resolve microsecond-scale dynamics. The improvement was achieved with a home-built electrochemical flow cell. By minimizing parasitic capacitance due to liquid coupling to electrodes and eliminating noise pickup, the flow cell enabled low-noise, high bandwidth measurement of molecular events as short as 2 us. The apparatus was used to observe closing and opening motions of lysozyme. Preliminary results suggest that lysozyme has a distribution of possible velocities with the most probable speed approaching our experimental resolution.

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