From the first telescope, to the electrocardiograph (EKG), to functional magnetic resonance imaging (fMRI), advances in scientific instruments – the tools of the trade – can have a huge impact on the science. With each new technology a window opens to observe things that previously might only have been theory, or guesses. Very often, things are observed that were not considered at all. The first telescopes revealed planets that were unknown. Optical microscopes exposed the world of life beyond the vision of the human eye. Now a team at the University of Southern California Los Angeles (UCLA, USA) have taken a relatively new technology (since the 1980s) – the cryo-electron microscope (cryo-EM) – and used it to view a virus at the level of individual atoms for the first time.
As developed by Hong Zhou and colleagues, the new techniques using the cryo-EM start with flash frozen viruses taken in their native environment. That’s the cryo (super-cold) part of this microscopy. Perhaps the most important part, carried out by the electron microscope technology, is to capture a three-dimensional image of the atoms. This 3-D capability is what really sets this microscopy apart because it can be used to study the atomic structure of even the smallest biological specimens.
Visible light microscopes (the ones familiar to most people from school labs) work by capturing reflected light, but that is also their main limitation – they can only observe objects down to about 500 nanometers because of the sizes the wavelengths of light. To go below 500 nanometers other kinds of microscopes are used. For example, the electron force microscope (EFM) uses a probe the size of one or a few atoms to ‘touch’ the subject and record the vibrations. The most common approach uses electron microscopy, where a beam of electrons is directed at the subject and a camera records the reflected electrons.
In the electron microscopy used at UCLA, the beams of electrons are shot from many directions, which multiple cameras record and composite into a three-dimensional image. This type of microscope operates in a vacuum, which helps retain the focus of the electron beams. Likewise the cryogenically frozen subjects (the viruses) are stable (have little or no extraneous vibration to cloud the picture). The result is a three-dimensional image of exceedingly high quality.
“This is the first study to determine an atomic resolution structure through Cryo-EM alone,” said Xing Zhang, a postdoctoral candidate in Zhou’s group and lead author of the Cell paper. “By proving the effectiveness of this microscopy technique, we have opened the door to a wide variety of biological studies.”
[Source: Nanotechnology Today]
As is often the case, the first experiments with the new equipment and techniques are interesting but not ground breaking in themselves. The researchers concentrated on water based viruses (aquareovirus) to examine the detailed structure, looking for the way this type of virus uses protein to attach itself (infect) a living cell. They were able to observe that this type of virus begins with a covering shell, which it sheds, and then uses ‘fingers’ of protein to contact and then attach to target cells.
Quite literally the cryo-electron microscope and the techniques developed for it are taking biology to a whole new level – atomic biology. Chemical and structural models of biological systems are currently drawn up at the molecular level. Now they can go to the atomic scale. Making sense of this kind of detail won’t be easy. There’s plenty of work yet to be done at the molecular level, and it may be decades before biologists have a completely workable set of frameworks to analyze the many kinds of biological subjects at the atomic level. Nevertheless, the ability to see biological structures at this incredibly small and detailed level entails the promise of understanding biology in a new way – and, of course, of being able to develop experiments (for example, with ways to use viruses for drug delivery in medicine) that may lead to techniques only barely imagine at the moment.