Studying the dynamics of how molecules fold and unfold has always been a struggle for Scientists due to their small size and rapid movement. Researchers from The Scripps Research Institute have collaborated with the University of California San Diego (UCSD) to develop a technique, referred to as temperature-jump, which allows the movement of these molecules to be studied.

This method involves the use of high temperatures to denature and unfold the molecule before dropping it again suddenly causing it to refold. The temperature jump is carried out so quickly that even the fastest molecular changes can be visualized.

There have been methods developed in the past to study bimolecular dynamics, however an effective method using temperature change was lacking. Temperature techniques created previously displayed two main problems: the limited size of the temperature drop and a lack of method to cool the samples again.

The device created is a small block of silicone containing minuscule channels for a solution containing the molecule to pass through. A novel feature is an observation channel, lined with sapphire to conduct heat away quickly and thin gold plating which acts to absorb the infrared from the laser beam to convert it into heat. These features allow for both limitations present for older techniques to be overcome. Small heating volume and the gold plating allows for the temperature to increase 50 degrees rapidly, were as the sapphire allows the molecule to cool rapidly.

The first example molecule to be studied by the research group was DNA which can fold into a hairpin loop in as little as a few microseconds (see Figure 1 below). Priya R. Banerjee, a research associate in Deniz's laboratory said that the group could not have observed such a rapid folding with previous temperature-jump systems, which typically take thousands of microseconds to cool molecules. The experiment allowed for the direct probing of the folding and unfolding dynamics of DNA hairpins following direct and indirect inverse temperature jumps.



Figure 1: DNA folded into a hairpin loop (image coutesy of RCSB Protein Data Bank)

The group will now use the technique to study the folding and unfolding kinetics of misfolded proteins associated with diseases including Huntington's and Alzheimer's.

More information on the experiment can be found in by reading the paper published in Nature: