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mitosis

The Perfect Cytoskeletal Storm

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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 [1]. Then, using time-lapse microscopy, the researchers watch the mechanical behavior of GFP-labeled microtubules [2] 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!

References:

[1] 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.

[2] 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.

Links:

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: Making Multicolored Waves in Cell Biology

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Bacteria are single-cell organisms that reproduce by dividing in half. Proteins within these cells organize themselves in a number of fascinating ways during this process, including a recently discovered mechanism that makes the mesmerizing pattern of waves, or oscillations, you see in this video. Produced when the protein MinE chases the protein MinD from one end of the cell to the other, such oscillations are thought to center the cell’s division machinery so that its two new “daughter cells” will be the same size.

To study these dynamic patterns in greater detail, Anthony Vecchiarelli purified MinD and MinE proteins from the bacterium Escherichia coli. Vecchiarelli, who at the time was a postdoc in Kiyoshi Mizuuchi’s intramural lab at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), labeled the proteins with fluorescent markers and placed them on a synthetic membrane, where their movements were then visualized by total internal reflection fluorescence microscopy. The proteins self-organized and generated dynamic spirals of waves: MinD (blue, left); MinE (red, right); and both MinD and MinE (purple, center) [1].


“OMG” Microscope Lives Up To Its Name

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Photo of an epithelial cell in metaphase with microtubules stained red, kinetochores stained green, DNA stained blue

Courtesy of Indiana University

The scientists at the IU School of Medicine-Bloomington nicknamed their new microscope the “OMG” for good reason—the images it produces are showstoppers. The DeltaVision OMX imaging system (its official title) is a $1.2 million dollar microscope that can peek inside a cell and image fluorescent proteins in unprecedented detail.

Jane Stout, a researcher in the NIH-funded lab, used the OMG to create this spectacular image that won her first place in the high- and super-resolution microscopy category of the 2012 GE Healthcare Life Sciences Cell Imaging Competition.

What you’re looking at is a cell in the midst of dividing into two identical copies—a process called mitosis. Here, the chromosomes (in blue) are aligned at the cell’s equator. Microtubules (red) from opposite poles of the cell attach to the chromosomes using the kinetochores (green) and pull them to opposite ends of the cell, which then splits in half. But sometimes cells do not divide properly—a common problem in cancer. Understanding the mechanics of cell division could help us correct this process when it goes wrong.

Jane Stout’s prize: her mitosis image will light up a billboard in Times Square in New York City in April. That is a wonderful celebration of science!

NIH support: the National Institute of General Medical Sciences