To 'See' Atoms for First Time
Cryo-EM 3-D Reconstruction of Aquareovirus
UCLA researchers (USA) report in the journal Cell that they have imaged a virus structure at a resolution high enough to effectively "see" atoms, the first published instance of imaging biological complexes at such a resolution. The research team, led by Hong Zhou, UCLA professor of microbiology, immunology and molecular genetics, used cryo-electron microscopy to image the structure at 3.3 angstroms. An angstrom is the smallest recognized division of a chemical element and is about the distance between the two hydrogen atoms in a water molecule.
The study, the researchers say, demonstrates the great potential of cryo-electron microscopy, or Cryo-EM, for producing extremely high-resolution images of biological samples in their native environment.
With traditional light microscopy, a magnified image of a sample is viewed through a lens. Some samples, however, are too small to diffract visible light (in the 500 to 800 nm range, or 5,000 to 8,000 angstroms) and therefore cannot be seen. To image objects at the sub-500 nm scale, scientists must turn to other tools, such as atomic force microscopes, which use an atomically thin tip to generate an image by probing a surface, in much the same way a blind person reads by touching Braille lettering.
With electron microscopy, another sub-500 nm technology, a beam of electrons is fired at a sample, passing through empty areas and bouncing off dense areas. A digital camera reads the path of the electrons passing through the sample to create a two-dimensional projection image of the sample. By repeating this process at hundreds of different angles, a computer can construct a three-dimensional image of the sample at a very high resolution.
Zhou is faculty director of the Electron Imaging Center for Nanomachines (EICN) at UCLA's California NanoSystems Institute, which is using cryo-electron microscopy to create 3-D reconstructions of nano-machineries, nano-devices and biological nano-structures, such as viruses.
Structurally accurate 3-D reconstructions of biological complexes are possible with cryo-electron microscopy because the samples are flash frozen, which allows them to be imaged in their native environment, and the microscope operates in a vacuum, because electrons travel better in that environment.
The Cell paper focused on a structural study of the aquareovirus, a non-envelope virus that causes disease in fish and shellfish, in an effort to better understand how non-envelope viruses infect host cells.
Zhang X., et. al.: 3.3 Å Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry. Cell, Volume 141, Issue 3, 472-482, 15 April 2010