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Posted: Feb 03, 2011
A revolution in structural biology: X-ray laser imaging of single particles
(Nanowerk News) An international interdisciplinary consortium of more than 20 laboratories (1) , including the CNRS laboratory Information Génomique et Structurale, has achieved an extraordinary feat: producing an ultra powerful X-ray laser beam to visualize a single viral particle in a single flash lasting several femtoseconds (10-15 seconds). The researchers have in fact converted the Stanford particle accelerator (SLAC) into a gigantic radiology instrument for "unique" particles: entire cells, viruses or even macromolecules.
This work, published on 3 February 2011 in the journal Nature ("Single mimivirus particles intercepted and imaged with an X-ray laser"), heralds a new era for structural biology by opening the way to the use of X-rays in the study of the three-dimensional structure of biological objects that are asymmetrical, non-crystallizable and even in movement. The team is now seeking to improve the resolution of the images in order to achieve detailed visualization of both the inside and outside of these biological particles.
The physicists involved in this work have been studying the possibility of using particle accelerators for biological studies since the mid-1990s. They have succeeded in adding a 800-meter long magnet structure to the Stanford Linear Accelerator (SLAC) so that the acceleration of electrons could lead to the emission of a colossal quantity of photons at the same frequency in hard X-ray wavelengths. These photons thus make up the most powerful X-ray laser beam in the world. The power supplied by this instrument, known as the LCLS (Linac Coherent Light Source), is 6.5 1015 watts/cm2, i.e. a ten billion-fold increase compared to the brilliance levels available until now! This figure is difficult to grasp considering that a nuclear power plant reactor "only" generates 1000 megawatts (1012 watts)… In addition, the laser pulse is very brief: 70 femtoseconds. All the energy directed into the target is thus concentrated in an extremely short time frame, which makes it possible to obtain an image before the explosion of the sample. Each biological particle injected into the beam of photons, at a speed of 300 km/h, is transformed into plasma at a temperature of 100,000 degrees Kelvin. But, before doing so, it has had time to diffract 1.7 million photons, from which its image is recreated using mathematical methods and software developed by the team of researchers.
The biological aspects of this work were dealt with by Chantal Abergel's team in the CNRS laboratory Information Génomique et Structurale headed by Jean-Michel Claverie (professor at the Université de la Méditerranée). The physicists actually wanted to validate this work on a biological object as "spectacular" as their laser. The researchers in Marseille therefore supplied the object of the study, the Mimivirus (2) particle, and were responsible for the preparation and the optimization of the samples needed for the experiments.
This work confirms the feasibility of using a particle accelerator as a structural biology tool to obtain, in a single laser "flash", a photograph of unique particles (viruses, bacteria, proteins, cells, etc.) and represents a "historical" step forward in the structural biology field. Indeed, until now, two techniques had been used to study biological objects: radiocristallography and electron microscopy. However, the requirements of these techniques (the targets must be "crystallizable", symmetrical, static and of suitable size) (3) exclude most biological objects and distort the results as they assume that all molecules are identical and impose a symmetry that is often not real. With the LCLS laser, each particle can be studied individually, whatever its size or properties. This technique thus heralds a new era: the structural biology of unique objects. Europe is preparing to take up this new challenge with its own tool, called ELI (Extreme Light Infrastructure), on which work has just begun (4).
The LCLS laser will make it possible to study both the surface and the inside of particles, since X-rays can pass through the samples. The current resolution of the images obtained is several nanometers (1 nm = 10-9 m). The researchers are currently working to optimize these performances and achieve a resolution of the order of several angstroms (1 Å = 10-10 m). The experiments planned over the coming months should make it possible to obtain the complete three-dimensional structure (internal capsid and nucleocapsid) of a Mimivirus particle at the nanometric scale and to compare several Mimivirus particles. Researchers could thus explore, for the first time, the existence of structural polymorphism of viral particles.
(1) The consortium is headed by Janos Hajdu of Uppsala University in Sweden.
(2) The Mimivirus, discovered in 2003 by the CNRS teams of Didier Raoult and Jean-Michel Claverie in Marseille, is the largest DNA virus known to date.
(3) Radiocristallography uses the crystallization of a large number of identical objects into a regular lattice to amplify their individual diffraction signals. Electron microscopy uses the symmetries (real or approximate) of objects to reconstitute their three-dimensional structure from a multitude (tens of thousands) of images of their projection onto a plane.
(4) See CNRS press release: http://www2.cnrs.fr/presse/communique/1920.htm