New imaging techniques let scientists see biomolecules more clearly

Feb 23 2009

Scientists have always wanted to take a closer look at biological systems and materials. From the magnifying glass to the electron microscope, they have developed increasingly sophisticated imaging devices.

Now, Niels de Jonge, Ph.D., and colleagues at Vanderbilt University have added a new tool to the cell biologist's toolbox. In the Proceedings of the National Academy of Sciences of the United States of America (PNAS), they describe a technique for imaging whole cells in liquid with a scanning transmission electron microscope (STEM).

"Electron microscopy is the most important tool for imaging objects at the nanoscale, including the size of molecules and objects in cells," said Dr. de Jonge. But electron microscopy requires a high vacuum, which has prevented the imaging of samples in liquid, such as biological cells. The new technique-liquid STEM-uses a microfluidic device with electron transparent windows to enable the imaging of cells in liquid.

In the current work, the investigators demonstrate imaging of individual molecules in a cell, with significantly improved resolution and speed compared with existing imaging methods. As an example, the investigators used liquid STEM to image single molecules of epidermal growth factor bound to a cell-surface receptor, achieving resolution as low as 4 nanometers.

"Liquid STEM has the potential to become a versatile tool for imaging cellular processes on the nanometer scale," Dr. de Jonge said. "It will potentially be of great relevance for the development of molecular probes and for the understanding of the interaction of viruses with cells."

In a separate paper published in the PNAS, Dan Rugar, Ph.D., and John Mamin, Ph.D., and their colleagues at IBM's Almaden Research Center describe their success in developing a magnetic resonance force microscope that can produce a structurally detailed image of viruses and other large biomolecules. The investigators predict that their new nanoscale magnetic resonance imaging (MRI) device eventually will be able to supplement x-ray crystallography as the predominant tool for determining the molecular structure of complex biomolecules, including those embedded in membranes.

At the heart of this device lies an ultrasensitive silicon cantilever that can detect the miniscule changes in magnetic force that develop when molecules are excited by an oscillating radiofrequency field while in a magnetic field. This new imaging device relies on the same physical principles that make MRI and nuclear magnetic resonance spectroscopy possible.

The work from Dr. de Jonge's group was detailed in the paper "Electron microscopy of whole cells in liquid with nanometer resolution." Investigators from Oak Ridge National Laboratory, University of Tennessee at Knoxville, University of Illinois at Urbana-Champaign, and Howard Hughes Medical Institute also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract

The work from IBM was described in the paper "Nanoscale magnetic resonance imaging." An abstract of this paper is available at the journal's Web site. View abstract