Cool Videos: Pushing the Limits of Live-Cell Microscopy


If you’re not watching recent work in biology, you might have thought that light microscopy hit its limits years ago.  After all, it’s been around a long time. But to the contrary, microscopic imaging technology just keeps getting better and better. Here you can look with unprecedented clarity at just one of the many dynamic processes going on within a living cell. Specifically, this video shows actin fibers (orange-red), which are key components of the cell’s cytoskeleton, slowly pulling clathrin-coated pits (green), which are basket-like structures containing molecular cargo, away from the cell’s external membrane and deeper within the cell.

This remarkable live-action view was produced using one of two new forms of extended-resolution, structured illumination microscopy (SIM). SIM is faster than other forms of super-resolution fluorescence microscopy. It’s also less damaging to cells, making it the go-to method for live-cell imaging. The downside has been SIM’s limited resolution—just twice that of conventional light microscopes. However, Nobel Prize-winner Eric Betzig and postdoc Dong Li of Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, along with colleagues including Jordan Beach and John Hammer at NIH’s National Heart, Lung, and Blood Institute, recently came up with two different solutions to enhance SIM’s spatial resolution.

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Snapshots of Life: Cell Skeleton on the Move


Credit: Torsten Wittmann, University of California, San Francisco

Cells are constantly on the move. They shift, grow, and migrate to new locations—for example, to heal a wound or to intercept an infectious agent as part of an immune response. But how do cells actually move?

In this image, Torsten Wittmann, an NIH-funded cell biologist at the University of California, San Francisco, reveals the usually-invisible cytoskeleton of a normal human skin cell that lends the cell its mobility. The cytoskeleton is made from protein structures called microtubules—the wispy threads surrounding the purple DNA-containing nucleus—and filaments of a protein called actin, seen here as the fine blue meshwork in the cell periphery. Both actin and microtubules are critical for growth and movement.

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Snapshots of Life: Visualizing Blood Vessels

Blood Vessels

Credit: Christopher V. Carman and Roberta Martinelli, Harvard Medical School, Boston

This might look a bit like a fish net, but what’s actually caught in this image is the structure of the endothelium—the thin layer of cells lining your blood vessels that controls the flow of molecules in and out of the bloodstream. The red lines are the actin filaments that give each endothelial cell its shape, while the purple are proteins called cadherins.

Most of the time, the actin “ropes” and cadherin “glue” act together to form a tight seal between endothelial cells, ensuring that nothing leaks out of blood vessels into surrounding tissue. However, when endothelial cells sense an infection or an injury, the cadherins open gaps that allow various disease-fighting or healing factors or cells present in the blood to breach the barrier and enter infected or injured tissue. After the infection subsides or wound heals, the gaps close and the blood vessel is once again impenetrable.

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The Beauty of Smooth Muscle

We humans have long wondered how, exactly, we develop from embryos into adults. This photo of an embryonic smooth muscle cell hints at the tremendous complexity of this fundamental biological mystery. And for those of you who might be wondering just what smooth muscles are, they’re the involuntary muscles found in places like the walls of our blood vessels, the digestive tract, the bladder, and the respiratory system.

This exquisite photo was produced using laser scanning confocal microscopy — a precise imaging method that includes the dimension of depth for scientific analysis. Here, green is used to label thin filaments of the protein actin, which is a key component of the cell’s cytoskeleton, and blue indicates another protein, called vinculin, which is enriched in locations involved in cell-cell adhesion.

Slowly but surely, using all the technology and tools available to us, we are unraveling the mysteries of biology — and turning our discoveries into health.

Science Becomes Art

Illustration of a human bone cancer cell

Credit: Dylan T. Burnette, NICHD, NIH

This stunning picture of a human bone cancer cell won artistic accolades: 3rd place in the Nikon Small World Competition. DNA, the blueprint of life, is actually blue in this photo. The yellow squiggles are little powerhouses called mitochondria that generate ATP ‘fuel’ for the cell. The purple wisps are filaments of actin, which help the cell move, keep its shape, and traffic chemicals from one part of the cell to another.

Happy New Year everyone.