Novel SLAC images combine art, science

Feb. 11, 2011, 2:01 a.m.

The world’s largest X-ray machine is capturing images of some of life’s smallest compounds at one quadrillionth of a second.

A collaborative group of researchers published two studies in Nature on Feb. 3 that gave a first look at femtosecond imaging of single particles and nano-sized crystals. Femtosecond imaging is a photography technique that uses very brief pulses.

(ANASTASIA YEE/The Stanford Daily)

Using the SLAC National Accelerator Laboratory’s Linac Coherent Light Source (LCLS), the group obtained a 2-D picture of the world’s largest virus, the mimivirus, in a single shot. The group also used the LCLS to develop a 3-D image of Photosystem I, a protein membrane system involved in photosynthesis, from nanoscale protein crystals.

The group’s nanocrystallography experiment was a “proof of principle,” said Stanford physicist and study co-author Marvin Seibert. When researchers compared their LCLS image to its previously known structure, they found that the two images matched. This, in turn, gave credibility to the process of femtosecond nanoscale crystallography.

Prior to the development of the femtosecond imaging, researchers had to grow proteins in large crystals to photograph them with conventional X-ray sources. According to Seibert, this process would take up to 13 years to yield results.

“Crystallography is more art than science,” Seibert said. “It’s literally trial and error.”

Conventional X-rays often can only process large-scale crystals because the rays destroy small samples before they can be analyzed. The beauty of femtosecond imaging, however, is in detecting beat destruction.

This technology is photography “taken to the extreme,” Seibert said.

“When you do high speed photography, you have a dark image and open the shutter just as a flash of light illuminates the sample,” Seibert said.

Similarly, “the photon pulse [of the LCLS] comes along as a very bright light that illuminates the dark sample and diffracts onto detectors,” he said.

The success behind the imaging in the two experiments rested in their ability to reduce the pulse to a femtosecond.

The pulse lasts only a femtosecond and the photons diffract off the sample before the molecule explodes from the radiation. The group can use the diffracting patterns to construct its image, because damage to the crystal becomes detectable after the photons have come in contact with the sample, Seibert said.

Researchers compiled tens of thousands of images to construct 3-D images of proteins in nanocrystallography. The 2-D mimivirus image, however, requires only one shot, hence the name “single particle” imaging.

The shorter time also allowed the researchers to reduce sample size.

“You don’t need any crystal at all [for the mimivirus],” Seibert said.

The 3-D proteins only require very small nanoscale crystals, as opposed to the one large crystal required in the past.

However, nanoscale imaging is not without its complications. Coordinating the samples, photon beam and detector requires precision.

“It’s not as extreme as a satellite launch, but then again it is not as expensive and not as many people [are involved],” Seibert said.

Due to the success of these images, the Coherent X-ray Imaging instrument (CXI) is now being developed specifically for imaging single particle and nanoscale crystals with SLAC’s LCLS.

“This will hopefully open up the technique to image 3-D structures from non-crystalline biological molecules,” Seibert said.

Currently, scientists know the shape of only six of the 30,000 membrane proteins in the human body. Thus, the CXI has the potential to significantly enhance research’s ability to produce images of more proteins. It is hoped that these images will be used to build a better understanding of bimolecular processes and structure-based drug design.

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