A Cell’s ‘Cap’ of Bundled Fibers

Researchers from the Johns Hopkins Engineering in Oncology Center have recently shown that in healthy cells, a bundled ”cap” of thread-like fibers holds the cell’s nucleus in its proper place. The nucleus includes the cell’s genetic storehouse, and understanding the nature of this cap and its influence could provide crucial clues, helping clinicians to diagnose and treat various diseases such as cancer and muscular dystrophy.
 A misshapen nuclei are an indicator of disease. (Source: Wikimedia Commons)
A misshapen nuclei are an indicator of disease. (Source: Wikimedia Commons)

Scientists have known for a long time that misshapen nuclei are an indicator of disease but they were not certain how a cell controlled the shape of its nucleus, the structure in mammal cells where genetic material resides. Now, a team led by principal investigator Denis Wirtz, professor of chemical and biomolecular engineering and director of the Engineering in Oncology Center, has published a study that claims to discover a fibrous structure. This structure holds the nucleus in its place, and it is called the perinuclear actin cap.

According to the study, published in the recent November 10th issue of Proceedings of the National Academy of Sciences, the perinuclear actin cap was discovered during the team’s efforts to understand whether cell shape controls nucleus shape. Their methods involved growing cells on a surface with alternating sticky and non-sticky stripes; then the researchers noticed that when cells grew along a sticky stripe, their nuclei elongated as well.

The next stage was to use a confocal microscope (a special kind of microscope that is capable of viewing an object one “slice” at a time). Shyam Khatau, a doctoral student, observed the reconstruction of the cell in three dimensions. Combining the images gave him the ability to produce short movies, showing the 3-D structure of the cells, the nucleus and the perinuclear actin cap.

“Under a microscope, the nucleus of a sick cell appears to bulge toward the top, while the nucleus of a healthy cell appears as a flattened disk that clings to the base,” said principal investigator Wirtz. When asked about the study’s goals, he said: “if we can figure out how and why this shape-changing occurs, we may learn how to detect, treat or perhaps even prevent some serious medical disorders.”

In their paper, the scientists describe a configuration which pushes the nucleus down toward the base of the cell; moreover, it creates the distinctive flattened shape of normal cells. “In healthy cells, the perinuclear actin cap is a domed structure of bundled filaments that sits above the nucleus, sort of like a net that is tethered all around to the perimeter of the cell membrane,” Wirtz said.

 Doctoral student Shyam Khatau, left, and Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center, played a key role in finding a bundled ‘cap’ of thread-like fibers that holds a cell’s nucleus in its proper place. (Source: Photo by Will Kirk, Homewood photo.jhu.edu)
Doctoral student Shyam Khatau, left, and Denis Wirtz, director of the Johns Hopkins Engineering in Oncology Center, played a key role in finding a bundled ‘cap’ of thread-like fibers that holds a cell’s nucleus in its proper place. (Source: Photo by Will Kirk, Homewood photo.jhu.edu)

The cap’s role in disease became evident when Khatau tested cells without the gene responsible of producing lamin A/C, a protein found in the membrane of the nucleus of normal cells but absent in the nuclear membrane of cells from people with muscular dystrophy. Other defective cells, that lack this distinctive cap, include cells with cancer, muscular dystrophy or progeria. Such diseased cells may appear more rounded and bulbous.

The work, which was funded by the National Institutes of Health and the Muscular Dystrophy Association, is not done, as the team intends to continue pursuing future discoveries that might help cure diseased cells. “We next plan to study how the cap’s effect on the shape of the nucleus affects what genes the cells express,” says Wirtz.

TFOT has also covered a new method to eliminate the tumor risk of using stem cells, which might help cure various diseases and the development of a virus that fights cancer, made at the North Carolina State University. Other related TFOT stories include two studies made at Cornell University: One claims that it understands AIDS and cancer better through receptors, and the other reporting about new methods of filtering out cancer from the bloodstream.

For more information about the JHU’s research of the cell’s nucleus, see the press release from John Hopkins University.