Researchers gain insight into abnormally shaped cell nuclei of people with cancer

February 19, 2013

Misshapen cell nuclei are frequently observed in the cells of people with cancer and other diseases, but what causes the abnormality—and why it is associated with certain disorders—has remained unclear.

Researchers at Northwestern University have recently developed a mathematical model that sheds light on the defect by clarifying the mechanisms that cause bulges known as "blebs" in cells' nuclear membranes. The research—a collaboration between experts at the McCormick School of Engineering and Applied Science and the Feinberg School of Medicine—could be a step toward bleb prevention, which may ultimately provide potential therapies for related diseases.

A paper describing the research, titled "Mechanical Model of Blebbing in Nuclear Lamin Meshworks," was published Feb. 11 in the USA.

"Changes in the shape of the nucleus are indicative of a range of pathologies, including the premature aging disorder Hutchinson-Gilford progeria syndrome, Emery–Dreifuss muscular dystrophy and some cancers," said Monica Olvera de la Cruz, the corresponding author of the paper. "Our research suggests that blebbing may be the result of an imbalance between the various proteins that constitute the nuclear lamina."

She is a Lawyer Taylor Professor, professor of materials science and engineering in the McCormick School and professor of chemistry in the Weinberg College of Arts and Sciences.

The nucleus—the control center of the cell, the keeper of genetic material and overseer of cell growth and reproduction—is covered by a nuclear envelope consisting of a double membrane and an underlying structure called the nuclear lamina that surrounds the surface of the nucleus and gives it shape. In addition to its mechanical support, the lamina helps regulate cell division and organize genetic material.

In the majority of healthy cells, the nucleus appears smooth and maintains an overall spherical shape, but abnormal nuclear shapes characterized by blebs have been observed in the cells of people suffering from some forms of cancer and other diseases.

In mammals, the lamin meshworks that make up the nuclear lamina consist of mainly two types of lamin proteins, known as types A and B, which are wrapped like two nets around the nucleus. Under normal conditions, the A-type and B-type lamins co-exist throughout the sphere, creating a healthy lamina of approximately even thickness throughout.

But when one of the B-type lamins is depleted, researchers found the A-type and B-type lamins begin to segregate from one another, resulting in an uneven mesh layer with altered mechanical properties. In some regions, the lamina's fibers begin to gap and separate, giving rise to nuclear blebs, bulges in the cell's nuclear envelope.

The nuclear lamins, especially the A-type lamins, are now considered to be major building blocks of nuclear architecture and are thus involved in numerous important nuclear functions. Much of the recent information on the functions of the nuclear lamins comes from findings demonstrating that many different human diseases are caused by hundreds of mutations in the nuclear lamin A gene. Many of these diseases are accompanied by changes in nuclear shape and altered lamin organization.

"This study helps us to begin to understand how these abnormal shapes are formed," said Robert D. Goldman, the Stephen Walter Ranson Professor of Cell and Molecular Biology, chair of the department of cell and molecular biology at the Feinberg School, and one of the paper's authors. "Collaborations between physicists and cell biologists are beginning to reveal new insights into these normal and abnormal ."

Enabling some of those new insights, the Northwestern researchers designed an energy-minimizing continuum elastic model that enabled them to produce structures with comparable shapes and patterns as those found in naturally occurring pathological nuclei.

Explore further: Mutation provides new insight into the molecular mechanisms of aging

Related Stories

Mutation provides new insight into the molecular mechanisms of aging

May 5, 2011
A new study identifies the mutation that underlies a rare, inherited accelerated-aging disease and provides key insight into normal human aging. The research, published by Cell Press online May 5 in the American Journal of ...

Genetic disease linked to protein build-up

August 29, 2012
Mutations of the gene Lmna previously thought to be directly responsible for a group of laminopathies—serious developmental conditions including premature aging and a form of muscular dystrophy—in fact cause them by allowing ...

Recommended for you

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.