- Scientists develop a new microscope that can image subcellular dynamics in multicellular organisms.
- To do this, they’ve combined Lattice light-sheet microscopy and Adaptive optics techniques.
- They were able to observe organelles’ behavior as they shape themselves within cells, in real time.
In 1665, Robert Hooke used a microscope to look at a small slice of cork and discovered small blocks, which he called ‘cells’. Since then, countless efforts have been made by many innovative minds to provide a better view of these building blocks of life.
Now researchers at Harvard Medical School and Howard Hughes Medical Institute have developed an advanced microscope that can capture exceptional details, including 3D pictures and videos of a living cell.
The microscope’s resolution is capable of imaging subcellular dynamics in multicellular organisms, like dynamics of vesicles (microscopic bubbles) that transport molecular cargo via cells.
For more than 3 centuries, researchers have used microscopes to observe cells. So far, the best visualizations have been obtained from cells isolated on glass slides. Observing cells in multicellular organisms in real-time, however, has remained a much more complex task.
Most of the time, target cells are surrounded by molecular structures or tissues that disturbs the beam of light entering from and going back to a microscope objective, blurring the crucial details. Using powerful beam isn’t a perfect solution because it could partially damage/distort tissues and other molecular structures.
So How Did They Do It?
To deal with these problems, researchers combined 2 techniques –
- Lattice light-sheet microscopy that increases the speed of image acquisition while reducing cell damage caused by phototoxicity.
- Adaptive optics that reduces the incoming wavefront distortions by actively shaping a mirror. It is generally used in astronomical telescope.
In lattice light-sheet microscopy, structured light sheet is used to excite fluorescence in a specimen’s consecutive planes. This produces a sequence of 3D pictures that provides insights of dynamic biological processes.
Whereas adaptive optics functions by analyzing the wavefront distortions and compensating for them with an instrument that fixes those errors like a liquid crystal array or a deformable mirror.
Simplified microscope schematic | Courtesy of researchers
They applied these principles in the field of microscopy with the help of two-photon laser that generates an adaptive optics set-up. As the lattice light sheet penetrates a multicellular organism, this set-up maintains the thin illumination of the sheet, generating distortion-free pictures of target cells.
Then they validated this microscope on various biological samples, and developed essential tools that visualize the information in effective ways. This includes fully-interactive 3D videos.
Cancer cell | Credit: Rick Groleau and Kevin Jiang
As you might have guessed by now, the outcomes were very impressive. You can see in the image, a cancer cell [shown in green] forcing its way through the blood vessel wall [purple] is clearly visible. The below image shows cells of a zebrafish eye in 3D.
Zebrafish eye’s cells | Credit: Liu et al
Researchers were able to visualize (in real-time) organelles’ behavior as they shape themselves within cells. In fact, they captured the near-molecular details of receptor-mediated endocytosis – a process in which cells absorb hormones, metabolites and other proteins.
Researchers are now working to make this technology simple and less-expensive. The current system fits in a 3 meter long table. The next version would be compact and affordable. Furthermore, the first microscope will be installed in Janelia Research Campus, where other scientists can use it.