PUBLIC DOMAIN, May 2020

NIH National Institute of Allergy and Infectious Disease

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The Virus that Ails Us Up Close and Personal

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Looking at SARS-CoV-2 magnified may help consumers understand why masks are temporarily important in the U.S. for keeping the virus out of the body.

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While these images play a major role in the way scientists learn to counteract pathogens and cure disease, that’s not exactly how viruses and bacteria look in our bodies. These images are “colorized” from black-and-white images—meaning they are digitally enhanced on a computer. At NIAID, capturing and enhancing these images takes a close collaboration of science and art.

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The parts of a cell include mitochondria, Golgi apparatus, cell membrane, and cell nucleus. A specially trained artist can color each of those cell parts to help the scientist identify, for example, how and where a virus or bacterium enters and attacks the cell. The fact that the final image happens to resemble a piece of art is an added bonus.

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The two most common types of images produced by NIAID scientists on heavy-duty electron microscopes show either the surface of a sample using a scanning electron microscope, or SEM, or show what’s happening inside a sample using a transmission electron microscope, or TEM. To understand how SEM images are produced, think of how satellites map the Earth by bouncing a signal back and forth. The process of producing TEM images is like shining a bright light at an object and then collecting a picture of the shadow behind the object. For electron microscopes, the electrons emitted in a beam create the SEM map and TEM shadows. SEM images are excellent for showing where and how a virus or bacteria may enter or leave a cell. TEM images are used to show what the virus or bacteria do once they are inside a cell—how they manipulate the cell to reproduce and spread.

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The process begins with a scientist explaining their project to a microscopist so they know how to prepare a sample and what types of images may answer a specific question. Prior to sharing their virus or bacteria samples with the microscopist, the scientist “fixes,” or kills, the virus or bacteria in the sample so there is no risk of infection.

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To prepare a typical SEM sample of infected cells, the microscopist receives “fixed” infected or uninfected cells on a small coverslip or silicon chip that serves as a mount for the microscope. The cells are further fixed with chemicals to keep structures intact. The cells must then be dried in a way that keeps them from collapsing under the vacuum in the electron microscope. The key to a good SEM sample is preserving key structural elements scientists need to study even with the water removed. The sample then is coated with a thin layer of metal so that the electrons don’t damage the sample during imaging.

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To prepare a TEM sample of chemically fixed viruses or bacteria, the microscopist can put a small droplet of suspended viruses or bacteria directly on a thin film. A chemical stain is then applied to help visualize the tiny viruses and bacteria under the TEM. Host cells that have been grown and infected with viruses or bacteria can be treated similarly to the SEM samples. Instead of completely drying the samples, the water is replaced with a dehydrating alcohol and then a liquid plastic. After samples are embedded in the plastic, they can then be sliced—like a microscopic loaf of bread—into 10,000 segments of a single millimeter. The microscopist then places a single slice of a sample on a small screen called a grid, which is about the size of a pinhead. They then navigate the grid under the microscope to locate desired regions of interest, often magnified several thousand times their original size. When they find something of interest, the microscopist takes a digital picture of the microscope image.

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After discussing the importance of each element of the image with the scientist, a visual artist then begins colorizing the images to help distinguish its important elements. The artists’ job requires a deep understanding of light in order to capture the highlights and shadows that bring out the dimensions of the microscopic image. Next, the artist works with the scientist to crop the image for the best composition around a scientific focal point. Finally, they select a color palette to enhance the details and create an engaging image.

These techniques were recently applied to help scientists visualize SARS-CoV-2, the novel coronavirus that causes COVID-19. For these images, the samples were magnified to between 30,000 and 90,000 times their actual size.