He films in the molecular world

When photographers converted sequences of still photographs to film, it was a big hit. Now, Richard Neutze wants to do the same thing - but at the molecular level. The goal is to make movies of the molecules that control our bodies, of the movements of proteins in cells. The camera consists of X-ray pulses that last a hundredth of a millionth of a millionth of a second!

Richard Neutze

Professor of Biochemistry

Wallenberg Scholar 

Institution:
University of Gothenburg

Research field:
Dynamics in the structure of membrane proteins.

Richard Neutze shows a series of pictures of a galloping horse, taken by the pioneering photographer Muybridge. In 1872, Muybridge helped the US businessman, Leland Stanford, with a now famous question: does a galloping horse ever have all of its hooves off the ground at any time? Muybridge set up cameras in a long row along a racetrack and rigged a trigger that caused every camera to take a picture as the horse galloped past. When this sequence of pictures was put together, it became a film. The horse undeniably flies in mid-gallop.

Richard Neutze's goal is to do the same thing: to use a still-photo technique to make movies. The experiments take place in California in the same stomping grounds on which Muybridge's horse galloped: a few kilometers outside Stanford University, founded by Leland Stanford.

“Stanford sponsored Muybridge to do this, and now Stanford University has built the first free electron laser,” says Richard Neutze, Professor of Biochemistry at the University of Gothenburg.

A three-kilometer long camera

The free electron laser, called the Linic Coherent Light Source, is the camera that Richard Neutze is using. When it was complete in 2009, it was unique in the world. It consists of a three-kilometer long tunnel through which researchers accelerate electrons that are ultimately converted to an X-ray laser beam of extremely high energy. Using this laser, Richard Neutze could follow the movements of proteins.

“Our bodies are controlled by what happens at a molecular level and we want to understand how this works,” he says.

Researchers have long used X-rays to take stills of proteins. They send the X-rays through crystals of proteins. Inside these crystals, proteins are packed in regular patterns, like water in an ice crystal or carbon atoms in a diamond. When X-rays pass through a crystal, they hit the proteins and are scattered.

Based on the pattern of the X-rays are scattered by the crystal, researchers can develop a three-dimensional picture of exactly what the protein looks like at an atomic level. The cool thing about the free electron laser is that it illuminates the protein crystal with an X-ray beam that is ten billion times stronger than the X-rays researchers have had access to so far.

“This gain is the difference between a slow walk and travelling at the speed of light,” says Richard Neutze.

The protein sample explodes - but the picture is caught anyway

At an X-ray free electron laser the X-ray pulse is so strong that the protein crystals explode. This explosion happens in less than a picosecond, which is why it should not be possible to use. But in 2000, when Richard Neutze together with his mentor at the time, Janos Hajdu at Uppsala University, began dreaming of photographing proteins with an X-ray laser, they worked out that if the pulse was really short, a few femtoseconds (one femtosecond is one thousandth of a millionth of a millionth of a second) would be enough to capture a picture of the crystal before it exploded.

When the world’s first X-ray free electron laser was constructed in 2009, Richard Neutze and Janos Hajdu were finally able to test their ideas in practice. The idea quickly proved to be accurate. It is possible to take pictures of proteins and the powerful beam provides a major advantage: protein crystals (which are often difficult to prepare) that a million times smaller than those useful at other X-ray sources, can be used at an X-ray free electron laser.

“We can focus the X-ray laser beam that is produced by a machine kilometers long, onto an object that is only 100 nanometers large. This technology is absolutely astounding,” says Richard Neutze.

His research team has already made use of this. They succeeded in taking a picture of a protein that is involved in trypanosomiasis. The crystals were extremely small and had never been possible to analyze with traditional technology.

“This was the first time that we learned something new from femtosecond crystallography. The journal Science picked up on this and named it one of the ten scientific breakthroughs in 2012,” says Richard Neutze.

Wants to film a protein that captures light

The next step is to make a movie. The target is a protein that captures light during photosynthesis. Tiny photosynthetic protein crystals will be sprayed in to the X-ray laser, but immediately before they are hit by the X-ray laser the researchers will shoot the protein crystals with visible light laser. The visible light activates the photosynthetic proteins and the goal is to make a three dimensional movie of the movements that arise within the crystals a few picoseconds after activation. By changing the time interval between the visible and X-ray laser beams, the researchers can capture different moments in the protein's movement, in the same way that Muybridge captured different moments in the horse's gallop.

»It is very rare to have such an opportunity like being named a Wallenberg Scholar. Among other efforts, we can modernize our lab and use the latest techniques instead of methods that are a decade old. Consequently, we can also take a step up and become more competitive in our research.«

Although Neutze's thoughts are similar to Muybridge's, there are major differences. Muybridge took around 15 pictures with his cameras. Richard Neutze will feed tens of thousands of tiny crystals into the femtosecond X-ray laser. Since these crystals turn and rotate as they are sprayed into the X-ray beam, he gets pictures from every which way. One single experiment leads to hundreds of thousands of pictures that, processed by a computer, yield a film that has something that Muybridge's film did not have: it is three dimensional.

Text Ann Fernholm
Translation Semantix
Photo Magnus Bergström

 

More about Richars Neutze's research