The Perfect Cytoskeletal Storm
Posted on by Dr. Francis Collins
Ever thought about giving cell biology a whirl? If so, I suggest you sit down and take a look at this full-blown cytoskeletal “storm,” which provides a spectacular dynamic view of the choreography of life.
Before a cell divides, it undergoes a process called mitosis that copies its chromosomes and produces two identical nuclei. As part of this process, microtubules, which are structural proteins that help make up the cell’s cytoskeleton, reorganize the newly copied chromosomes into a dense, football-shaped spindle. The position of this mitotic spindle tells the cell where to divide, allowing each daughter cell to contain its own identical set of DNA.
To gain a more detailed view of microtubules in action, researchers designed an experimental system that utilizes an extract of cells from the African clawed frog (Xenopus laevis). As the video begins, a star-like array of microtubules (red) radiate outward in an apparent effort to prepare for cell division. In this configuration, the microtubules continually adjust their lengths with the help of the protein EB-1 (green) at their tips. As the microtubules grow and bump into the walls of a lab-generated, jelly-textured enclosure (dark outline), they buckle—and the whole array then whirls around the center.
Abdullah Bashar Sami, a Ph.D. student in the NIH-supported lab of Jesse “Jay” Gatlin, University of Wyoming, Laramie, shot this movie as a part his basic research to explore the still poorly understood physical forces generated by microtubules. The movie won first place in the 2019 Green Fluorescent Protein Image and Video Contest sponsored by the American Society for Cell Biology. The contest honors the 25th anniversary of the discovery of green fluorescent protein (GFP), which transformed cell biology and earned the 2008 Nobel Prize in Chemistry for three scientists who had been supported by NIH.
Like many movies, the setting was key to this video’s success. The video was shot inside a microfluidic chamber, designed in the Gatlin lab, to study the physics of microtubule assembly just before cells divide. The tiny chamber holds a liquid droplet filled with the cell extract.
When the liquid is exposed to an ultra-thin beam of light, it forms a jelly-textured wall, which traps the molecular contents inside . Then, using time-lapse microscopy, the researchers watch the mechanical behavior of GFP-labeled microtubules  to see how they work to position the mitotic spindle. To do this, microtubules act like shapeshifters—scaling to adjust to differences in cell size and geometry.
The Gatlin lab is continuing to use their X. laevis system to ask fundamental questions about microtubule assembly. For many decades, both GFP and this amphibian model have provided cell biologists with important insights into the choreography of life, and, as this work shows, we can expect much more to come!
 Microtubule growth rates are sensitive to global and local changes in microtubule plus-end density. Geisterfer ZM, Zhu D, Mitchison T, Oakey J, Gatlin JC. November 20, 2019.
 Tau-based fluorescent protein fusions to visualize microtubules. Mooney P, Sulerud T, Pelletier JF, Dilsaver MR, et al. Cytoskeleton (Hoboken). 2017 Jun;74(6):221-232.
Mitosis (National Human Genome Research Institute/NIH)
Gatlin Lab (University of Wyoming, Laramie)
Green Fluorescent Protein Image and Video Contest (American Society for Cell Biology, Bethesda, MD)
2008 Nobel Prize in Chemistry (Nobel Foundation, Stockholm, Sweden)
NIH Support: National Institute of General Medical Sciences
Cool Videos: A Biological Fireworks Display
Posted on by Dr. Francis Collins
Let’s kick off the Fourth of July weekend with some biological fireworks! While we’ve added a few pyrotechnic sound effects just for fun, what you see in this video is the product of some serious research. Using a specialized microscope equipped with a time-lapse camera to image fluorescence-tagged proteins in real-time, an NIH-funded team has captured a critical step in the process of cell division, or mitosis: how filaments called microtubules (red) form new branches (green) and fan out to form mitotic spindles.
In this particular experimental system, the team led by Sabine Petry at Princeton University, Princeton, NJ, studies the dynamics of microtubules in a cell-free extract of cytoplasm taken from the egg of an African clawed frog (Xenopus laevis). Petry’s ultimate goal is to learn how to build mitotic spindles, molecule by molecule, in the lab. Such an achievement would mark a major step forward in understanding the complicated mechanics of cell division, which, when disrupted, can cause cancer and many other health problems.
Cool Videos: Fireworks under a Microscope
Posted on by Dr. Francis CollinsThis Fourth of July, many of you will spread out a blanket and enjoy an evening display of fireworks with their dramatic, colorful bursts. But here’s one pyrotechnic pattern that you’ve probably never seen. In this real-time video, researchers set off some fluorescent fireworks under their microscope lens while making an important basic discovery about how microtubules, the hollow filaments that act as the supportive skeleton of the cell, dynamically assemble during cell division.
The video starts with a few individual microtubule filaments (red) growing linearly at one end (green). Notice the green “comets” that quickly appear, followed by a red trail. Those are new microtubules branching off. This continuous branching is interesting because microtubules were generally thought to grow linearly in animal cells (although branching had been observed a few years earlier in fission yeast and plant cells). The researchers, led by Sabine Petry, now at Princeton University, Princeton, NJ, showed for the first time that not only do new microtubules branch during cell division, but they do so very rapidly, going from a few branches to hundreds in a matter of minutes .