Scientists identify how cells respond to mechanical force

July 8, 2011
Scientists identify how cells respond to mechanical force

Many aspects of cell behaviour are influenced by mechanical force, but how single cells respond to these forces is unclear. An EU-funded team of researchers sheds light on the relationship between the signals that affect cells' behaviour and their physical properties. The findings are published in the journal Nature Cell Biology.

Biologists and physicists led by the University of North Carolina at Chapel Hill (UNC-Chapel Hill) in the United States found that exerting on activates Rho-GEF proteins through distinct signalling pathways. According to the researchers, these Rho proteins are members of the Ras superfamily, a class of proteins linked to cancer activity. The team exerted force on the cells by using magnets and applying to the cells. This generated extracellular tension.

"The application of force on integrins triggers cytoskeletal rearrangements and growth of the associated adhesion complex, resulting in increased cellular stiffness, also known as reinforcement," the authors write. "Although RhoA has been shown to play a role during reinforcement, the that regulate its activity are unknown. By combining biochemical and biophysical approaches, we identified two guanine nucleotide exchange factors (GEFs), LARG and GEF-H1, as key molecules that regulate the cellular adaptation to force. We show that stimulation of integrins with tensional force triggers activation of these two GEFs and their recruitment to adhesion complexes."

Commenting on the success of the study, senior author Professor Keith Burridge, a researcher of cell and at UNC-Chapel Hill, says: "This experiment was only possible because we were able to bring together a team of physicists and cell biologists. It's very exciting because we have identified the entire pathway between the tension exerted on the cell to proteins that, in turn, activate other proteins that we know tend to be hyperactive in cancer."

Past studies postulated that the mechanical environment of cells impacts cell growth and properties. Solid tumor cells usually have an altered stiffness, for instance. Other studies discovered that the prognosis gets worse when the cell matrix becomes stiffer. Scientists have also proved that rigid tumours shed an increased number of cells, and they in turn escape the original tumor site, which potentially raises the risk of cancer spreading through metastasis.

"There has been a hypothesis that cell stiffness and tension create a vicious cycle leading to enhanced growth, more cell density, more tension, and larger tumors," Professor Burridge explains.

He goes on to say that the funding afforded to the researchers, including a grant from the University Cancer Research Fund in the United States, gave the team the support they needed to obtain their results. More work on this issue is planned by the researchers, helping to further elucidate the association between the signals that impact both the behavior and physical properties of cells.

Explore further: Cell rigidity linked to activity in proteins associated with cancer

More information: Guilluy, C., et al. (2011) 'The Rho GEFs LARG and GEF-H1 regulate the mechanical response to force on integrins'. Nature Cell Biology. DOI: 10.1038/ncb2254

Related Stories

Stretch a DNA Loop, Turn Off Proteins

December 5, 2006

It may look like mistletoe wrapped around a flexible candy cane. But this molecular model shows how some proteins form loops in DNA when they chemically attach, or bind, at separate sites to the double-helical molecule that ...

Researchers hot on the trail of brain cell degeneration

March 19, 2007

A research team headed by Academy Research Fellow Michael Courtney has identified a new molecular pathway in neurons. The pathway is a factor in the degeneration of brain cells, which in turn plays an important role in neurological ...

Normalizing tumor vessels to improve cancer therapy

August 25, 2008

Chemotherapy drugs often never reach the tumors they're intended to treat, and radiation therapy is not always effective, because the blood vessels feeding the tumors are abnormal—"leaky and twisty" in the words of the ...

Recommended for you

Scientists create first stable semisynthetic organism

January 23, 2017

Life's genetic code has only ever contained four natural bases. These bases pair up to form two "base pairs"—the rungs of the DNA ladder—and they have simply been rearranged to create bacteria and butterflies, penguins ...

Lab charts the anatomy of three molecular channels

January 23, 2017

Using a state-of-the-art imaging technology in which molecules are deep frozen, scientists in Roderick MacKinnon's lab at Rockefeller University have reconstructed in unprecedented detail the three-dimensional architecture ...

New steps in the meiosis chromosome dance

January 23, 2017

Where would we be without meiosis and recombination? For a start, none of us sexually reproducing organisms would be here, because that's how sperm and eggs are made. And when meiosis doesn't work properly, it can lead to ...

Research describes missing step in how cells move their cargo

January 23, 2017

Every time a hormone is released from a cell, every time a neurotransmitter leaps across a synapse to relay a message from one neuron to another, the cell must undergo exocytosis. This is the process responsible for transporting ...

Immune defense without collateral damage

January 23, 2017

Researchers from the University of Basel in Switzerland have clarified the role of the enzyme MPO. In fighting infections, this enzyme, which gives pus its greenish color, produces a highly aggressive acid that can kill pathogens ...

Provocative prions may protect yeast cells from stress

January 23, 2017

Prions have a notorious reputation. They cause neurodegenerative disease, namely mad cow/Creutzfeld-Jakob disease. And the way these protein particles propagate—getting other proteins to join the pile—can seem insidious.


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.