by Olcay Sahin
There are days when everything feels squeezed together: messages popping up, work to finish, family to look after. We keep passing tasks from one hand to the other and hope nothing drops. Cells face a similar kind of pressure on a much smaller scale. Every time a cell divides, it faces a difficult packing problem. It doesn’t just need to copy its genes and send them to the next generation. It also must decide what to do with thousands of tiny inner power plants, the mitochondria: reshape them, move them around, and pass them on so that both new cells can keep running.
During this brief moment, mitochondria are doing far more than just sitting in the background. They help fuel the machinery that pulls chromosomes apart and decide how much energy and stress‑handling capacity each new cell will inherit. If this handover goes wrong, cells can stall in division, slip into death, or quietly carry damage forward into the tissue (1).
For people who study cells, this handover is hard to resist watching. If we could see how these power plants move and change as a cell splits, we might understand why some cells stay healthy under stress while others tip toward disease. But there is a catch: the way we usually watch can quietly change the very thing we are trying to see.
This is where the shy animals come in.
Watching mitochondria with different microscopes is a bit like trying to watch shy animals in a forest at night. One option is to walk in with a bright flashlight. That is what classic glowing‑label imaging does: we paint the animals with glowing paint and then shine strong light, so they light up. We do see them, but the light scares them, changes how they move, and, if we keep it on for too long, can even hurt them. In cells, that bright light and those labels can damage the inner power plants and disturb the way the cell splits, so the story we record is no longer the cell’s real one.
Here, the scientists simply decide to stop shining the torch on the animals’ faces. They use a kind of night‑vision that pays attention to tiny changes in how the forest bends the light that passes through it. Some spots look a bit thicker, some a bit thinner, and that quiet pattern is enough to tell who is moving where. By slowly collecting many of these gentle views, they can follow all the shy animals in the clearing without ever covering them in glowing paint.
Behind the scenes, that night‑vision is a holotomographic microscope. Instead of colours from dyes, it builds three‑dimensional maps of how strongly each tiny piece of the cell bends light, a property called the refractive index (2; 3). With a single, low‑power laser, it sends light through the cells from many different angles and then uses those holograms to reconstruct the full volume, so the mitochondria appear as bright, reticular structures in three dimensions without any fluorescent label.
In the real experiment, the “forest” is a thin layer of human cells that normally line blood vessels (4). These cells are flat and spread out, which makes their inner power plants easier to spot with this gentler camera. The researchers grow them in narrow microfluidic channels under a steady flow that mimics blood, so the cells settle into a protective state closer to what they would feel in a real vessel wall. Then they disconnect the flow and move the slide straight onto the holotomographic microscope, taking one three‑dimensional snapshot every two minutes for six hours which is long enough to follow complete rounds of cell division without obvious delays or damage. The main movie uses only this soft, no‑paint method. In a separate control, they add a tiny amount of glowing mitochondrial dye to a few cultures, just once, to check that the bright, reticular shapes they see in the refractive‑index maps really are mitochondria and voila they match.
As the movie plays, a pattern appears. In the calm phase before a split, the power plants weave a loose network around the center of the cell. As the cell gets ready to pull its genes apart, this network compacts and shifts, lining up along the direction where the cell will pinch. Later, as the two new cells begin to separate, the power plants stretch out again and spread into both sides, so that the next generation inherits a working network in each cell. In the holotomographic reconstructions, that whole dance shows up not as colours, but as a moving, reticular mass of higher‑density material wrapping and unwrapping around the dividing nucleus.
Equally important is what does not happen. The split finishes on time, instead of dragging on. The power plants stay smooth and continuous, instead of swelling up or breaking into tiny pieces – classic signs that the cell is stressed by how we are looking at it. That suggests that this time, the camera is not rewriting the story.
This gentle way of watching matters beyond this one movie. If we want reliable stories about how mitochondria support, fail, or adapt during cell division, we need tools that let cells live their own lives while we watch. A night‑style microscope that works without glowing paint offers exactly that: a low‑stress, long‑term view of how inner power plants are reshaped and passed on to the next generation. Because it can track refractive‑index changes as a stand‑in for mass and density, the same approach can be extended to other fragile structures – from tight junctions between endothelial cells to lamellipodia at the edge of a migrating cell – without adding anything that might disturb them (5). In the future, using this kind of label‑free, three‑dimensional “night‑vision” on cells from real patients could help us connect tiny shifts in these power plants to bigger stories about ageing blood vessels, heart disease, or even brain disorders.
References:
- Pedley, R., & Gilmore, A. P. (2016). Mitosis and mitochondrial priming for apoptosis. Biological Chemistry, 397 (7), 595–605. https://doi.org/10.1515/hsz-2016-0134
- Medina-Ramirez, I. E., Macias-Diaz, J. E., Masuoka-Ito, D., & Zapien, J. A. (2024). Holotomography and atomic force microscopy: A powerful combination to enhance cancer, microbiology and nanotoxicology research. Discover Nano, 19(1), 64. https:// doi.org/10.1186/s11671-024-04003-x
- Sbrana, F., Chellini, F., Tani, A., Parigi, M., Garella, R., Palmieri, F., Zecchi-Orlandini, S., Squecco, R., & Sassoli, C. (2024). Label-free three-dimensional imaging and quantitative analysis of living fibroblasts and myofibroblasts by holotomographic microscopy. Microscopy Research and Technique, 87(11), 2757–2773. https://doi. org/10.1002/jemt.24648
- Yuhasz, D., Shewandagn, B., & Jurney, P. (2026). Label‑free quantification of mitochondrial dynamics through mitosis using holotomographic microscopy. The Journal of Precision Medicine: Health and Disease, 5, 100029. https://doi.org/10.1016/j.premed.2026.100029
- Leineweber, W. D., Munares, G. A., Leycam, C., Michael, R., Noyer, J., & Jurney, P. (2025). Holotomographic microscopy reveals label-free quantitative dynamics of endothelial cells during endothelialization. European Journal of Cell Biology, 104(2), Article 151492. https://doi.org/10.1016/j.ejcb.2025.151492
Author-
Olcay Sahin is a molecular biologist from Türkiye with an MSc in Molecular Biology and Genetics. She is fascinated by epigenetics, genome maintenance, cell‑cycle control, and mitochondrial biology, especially in the brain, and her research experience in Strasbourg strengthened her belief that clear science communication is essential for researchers from different cultures to work together. Beyond the lab, she loves drawing and painting, journaling, and gathering small keepsakes as real‑world reminders of meaningful memories.
Images- AI generated
This article was written as part of Club SciWri’s Science Writing Workshop, an initiative aimed at nurturing new voices in science communication and helping participants explore how to make complex ideas accessible to wider audiences.
Workshop conducted by Saurja Dasgupta, Ananya Sen, Rohini Subrahmanyam, Sumbul Jawed Khan and Roopsha Sengupta
