Scientists will soon be able to get a peek at exactly what proteins do in the first few microseconds of folding. A report in an upcoming issue of Physical Review Letters explains how minute quantities of fluids can be mixed together in less than 10 microseconds, at least five times faster than the speediest mixing times to date. This will allow researchers to control chemicals that switch the folding mechanism on and off fast enough to catch a protein in the act of bending.
Just as milk blends into coffee much more quickly if the liquids are stirred, researchers speed chemicals into solution by shaking them. Until the turbulent mixture settles down, however, it is impossible to see what the protein is doing. Moreover, large quantities of often expensive samples are required if researchers want to mix samples by inducing turbulence. James Knight and his colleagues at Princeton University built on an idea put forth about 2 years ago that solved both these problems: To get fluids to combine faster, give them less room to mix. In other words, he says, use an incredibly tiny coffee cup.
To make their tiny mug, Knight and his colleagues etched four perpendicular channels a few micrometers deep and wide into a chip of silicon. The pressure from two side channels--filled with a solution of iodide--"squeezed" a fluorescent dye from both sides, squirting it into a stream as narrow as 50 nanometers. At such tiny scales, the iodide molecules mixed with the dye in less than 10 millionths of a second and used up only 25 billionths of a liter for 5 seconds' worth of data.
Researchers have already started doing experiments using the tiny mixing machine. Says William Eaton, a biophysical chemist with the National Institutes of Health, "This is potentially going to be one of the most powerful methods for studying protein folding." The quick speed and lack of turbulence will allow scientists to watch the first few microseconds of this complicated act.