Author: Natalia Khalatyan
Artist: Aurora Chen
When you Google “cell” and click on the Images tab, what do you see? Probably a bunch of colorful blobs with various other colorful blobs inside of them that are very distinct from one another due to their shapes, sizes, and features such as the mitochondrial matrix. If you are familiar with cellular organelles you can even tell most of them apart! However, those are extremely simplified depictions of reality to help us understand the cell’s basic principles.
Now, what if you Google “EM of the cell” what do you see? Various grayscale blobs that are not quite as pleasant to look at and you might have a harder time distinguishing one organelle from another. Yet scientists use EM, or electron microscopy, and other various microscopy techniques to make colorful schematics we are familiar with to help us understand our own biology. Kind of like looking at a photograph of your family at the beach instead of a doodle your 4-year-old cousin made.
Depending on the quality of your camera (or the resolution of the microscope) you can tell each family member apart. You can even zoom in on the graphic T your uncle is wearing to read the name of his favorite band. But what about the details of your family’s beach day? You can only piece it together based on stories you heard from your family so imagine trying to understand something that does not speak or make any sounds at all, like a cell. Where would you even begin?
Over the past several decades, microscopy techniques have advanced tremendously and aided scientists in understanding cells in various disease states (such as cancer), their basic cellular processes (like cell division), or even capture a virus infecting a cell (including SARS-CoV-2, the causative agent of Covid-19). Although electron microscopy will provide general details the reality is a lot more complex than that. The cell comprises thousands and thousands of different molecules of all shapes and sizes such as proteins, lipids, carbohydrates, and various combinations of all three. To better understand where and what these molecules do scientists can “mark” these specific molecules that will then fluoresce in a technique called fluorescent microscopy. Now if you Google that you will find remarkable images that might just take your breath away.
Fluorescent microscopy can even be used with live cells to create videos of what these molecules do over a course of several hours or even days. By marking more than one molecule you can track their interactions and if you’re lucky, see a unique phenomenon unravel right before your eyes. But microscopy doesn’t come with its limitations. Some molecules are just similar enough that when you try to mark one, you may unintentionally mark a different one or the molecule is so complex that there is no way of marking it, to begin with. In addition, the techniques used for imaging may jeopardize the natural pathways and mechanisms of the cell causing a phenomenon that would not normally exist.
Besides, how many takes did it take to get that perfect family photo at the beach? It probably took several and a bit of frustration due to your mother blinking at the last minute or your 4-year-old cousin getting antsy causing a blurry photo. Fortunately, you can start a countdown to prevent last-minute blinking or bribe your cousin with an ice cream cone if only she stood still for a few seconds. Yet you can’t quite do that with cells (wouldn’t that make life easier!). Microscopy imaging may take several days or weeks trying to find that one cell that looks just right, with all its marked molecules arranged in such a way that will help a viewer understand exactly what is going on. But in the end, it is well worth it since without microscopy imaging we would have no way of knowing how a healthy cell functions or even looks like, a major first step in any disease diagnosis and treatments.
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