Researchers from the Johns Hopkins Engineering in Oncology Center have shown that in healthy cells, a bundled “cap” of thread-like fibers holds the cell’s nucleus, its genetic storehouse, in its proper place.
Understanding this cap’s influence on cell and nuclear shape, the researchers say, could provide clues to the diagnosis and treatment of diseases such as cancer, muscular dystrophy and the age-accelerating condition known as progeria.
“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 Denis Wirtz, professor of chemical and biomolecular engineering and director of the Engineering in Oncology Center. “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.”
Scientists have known that misshapen nuclei are an indicator of disease, Wirtz said, but they were not certain how a cell controlled the shape of its nucleus, the structure in mammal cells where genetic material resides. In a study published in the Nov. 10 issue of the Proceedings of the National Academy of Sciences, however, the research team led by Wirtz reported the discovery of a fibrous structure that holds the nucleus in its place. The researchers call this new network structure the perinuclear actin cap.
“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. This configuration pushes the nucleus down toward the base of the cell and also creates the distinctive flattened shape of normal cells. Cells with cancer, muscular dystrophy or progeria, however, lack this distinctive cap, allowing the nucleus to float upward toward the top of the cell’s membrane. These diseased cells may appear more rounded and bulbous.
“The cap controls the shape of the nucleus by controlling the shape of the cell itself,” Wirtz said.
The perinuclear actin cap was discovered while the team was trying to find out if cell shape controls nucleus shape. By growing cells on a surface with alternating sticky and non-sticky stripes, the researchers noticed that as cells grew along a sticky stripe, their nuclei elongated as well. Using a confocal microscope -- a special kind of microscope that can view an object one “slice” at a time -- doctoral student Shyam Khatau was able to reconstruct the cell in three dimensions. By stacking the confocal microscope images together, Khatau, who is affiliated with the Johns Hopkins Institute for NanoBioTechnology, was able to produce short movies showing the 3-D structure of the cells, the nucleus and the perinuclear actin cap. (The movies are online at http://inbt.jhu.edu/outreach/media-library/video.)
“That’s when we saw the cap,” Khatau said, “and Dr. Wirtz realized we were on to something.”
The cap’s role in disease became evident when Khatau tested cells without the gene to produce 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. Cells without lamin A/C failed to produce the perinuclear actin cap.
“We next plan to study how the cap’s effect on the shape of the nucleus affects what genes the cells express,” said Wirtz.
Khatau, who is pursuing his doctorate in the Department of Chemical and Biomolecular Engineering, is lead author of the journal article. Additional Johns Hopkins authors on this paper are Wirtz; doctoral student Christopher M. Hale and senior Meet Patel from the Whiting School of Engineering’s Department of Chemical and Biomolecular Engineering; and Peter C. Searson, a professor in the school’s Department of Materials Science and Engineering. Other co-authors were P. J. Stewart-Hutchinson and Didier Hodzic from the School of Medicine at the Washington University in St. Louis and Colin L. Stewart from the Institute of Medical Biology, Singapore.
This work was funded by the National Institutes of Health and the Muscular Dystrophy Association.
Color images and video of the researchers available; contact Mary Spiro.Related Links:
Mary Spiro | Newswise Science News
First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife
Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
26.10.2016 | Physics and Astronomy
26.10.2016 | Earth Sciences
25.10.2016 | Earth Sciences