Any photographer can vouch for the difficulty of capturing a clear picture of a moving target. When it comes to molecules, however, sometimes the motion is exactly what scientists want to see - for example, to understand the pathological protein mis-folding and assembly that seem to underlie a host of human disorders, including diabetes and Alzheimer's disease.
Pancreatic damage in type 2 diabetes has been linked to toxic clumps of the protein hIAPP (human islet amyloid polypeptide), which is normally produced by the same cells that make insulin. An unknown trigger prompts the protein to fold into sharp fibres that poke holes in pancreatic cells, killing them. Though scientists already have a good idea of the healthy "before" and dangerous "after" hIAPP structures, the steps in between remain somewhat of a mystery, says University of Wisconsin-Madison chemistry professor Martin Zanni, who led the new study.
Zanni's research group used a method, known as two-dimensional infrared spectroscopy (2-D IR for short), that takes advantage of the restless nature of molecules and atoms. Proteins are constantly in motion, and their endless atomic twitching conveys information about their organization. Infrared laser beams can detect the minute vibrations and identify characteristic patterns to deduce protein structures.
A few years ago, Zanni's team built the first device capable of designing infrared laser beams with a computer. The team has now simplified and speeded up the process with an automated version of the 2-D IR technique. They obtained a single structural scan of hIAPP in less than a second - more than 500 times faster than previously possible. The speed is crucial for trying to understand a dynamic process like hIAPP mis-folding, Zanni says. "No matter how fast they're moving, we can take pictures of them," says Zanni.
MEDICA.de; Source: University of Wisconsin-Madison