Pierce, Daniel W. and Vale, Ronald D. (1999). Meth. Cell Biol. 58: 49-73.
The first measurement of the activity of a single protein molecule was reported for an ion channel using patch-clamp methods in 1976 (Neher and Sakmann, 1976) and spawned the vast enterprise of ion channel biophysics that exists today. Thirteen years elapsed before the second single molecule measurement, which was detection of the movement induced by a single kinesin molecule in 1989 (Howard et al. 1989; Block et al., 1990). Single-molecule measurements on motor proteins have also proliferated (Svoboda et al., 1993; Finer et al., 1994; Ishijima et al., 1994; Coppin et al., 1995; Meyhofer and Howard, 1995). What both these systems have in common is that a unique property of the enzyme was exploited to perform the measurement. Ion channels are essentially amplifiers of their own activity, allowing picoampere ion currents to flow in response to changes in membrane potential or the presence or absence of ligands. Motor proteins elicit movement, and the forces they produce are sufficient to move objects visible in the light microscope.
Research: Single Molecule Fluorescence Imaging and Assays