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
I developed an interest in the cytoskeleton in 1978 when I discovered a mutant beta actin in a fibrosarcoma cell line. I ultimately demonstrated that transfer of the mutant actin gene into a non-tumorigenic, immortalized cell converted it to a tumorigenic cell. In the same experiment I discovered a protein, which I later named L-plastin, which is an actin bundling protein induced in most cancer cell lines and solid tumors. Normally L-plastin is expressed only in leukocytes. I theorized that L-plastin expression contributed to the ability of cells from solid tissues to behave like white blood cells with less anchorage independence a key property of metastatic cells. Today both L- and T-plastin (isoforms) have been shown to contribute to metastasis.