In its June 2008 issue, Nature Methods presents a free-access focus on single-molecule techniques. Biologists are becoming increasingly interested in methodologies that can examine the mechanism of action of fundamental biological processes at the molecular level. The Nature Methods focus consists of four review articles that provide practical guidance for some of the techniques that are most integral to in vitro single-molecule experiments. These cover single-molecule fluorescence methods; microfluidic flow cells to manipulate experimental conditions during experiments; and force-spectroscopy techniques such as atomic force microscopy (AFM) and optical traps to manipulate individual molecules themselves.

From the focus’s Editorial: The ability to analyse biological systems at the single-molecule level opens avenues of investigation that are not possible using techniques that measure aggregate properties of molecular populations. This new vantage point can yield important insights. A textbook example is that of molecular motors. Although classical biological assays for motor function show that these molecules support constant-velocity movement, studies of individual molecules revealed that they take discrete individual steps. The technique that allowed these crucial biological observations came from the physics field in 1986—a momentous year that saw the first demonstration not only of the optical tweezers technique used in the subsequent molecular motor study but also of the atomic force microscope. Created by physicists, these force-spectroscopy methods form much of the backbone of the field of research now devoted to studying biological systems at the single-molecule level."

Please read on at the Nature Methods focus website. Comments from readers are welcome at Methagora, the Nature Methods blog.