Why cells stick: Phenomenon extends longevity of bonds between cells
Research carried out by scientists at the Georgia Institute of Technology and The University of Manchester has revealed new insights into how cells stick to each other and to other bodily structures, an essential function in the formation of tissue structures and organs. It's thought that abnormalities in their ability to do so play an important role in a broad range of disorders, including cardiovascular disease and cancer.
The study's findings are outlined in the journal Molecular Cell and describe a surprising new aspect of cell adhesion involving the family of cell adhesion molecules known as integrins, which are found on the surfaces of most cells. The research uncovered a phenomenon termed "cyclic mechanical reinforcement," in which the length of time during which bonds exist is extended with repeated pulling and release between the integrins and ligands that are part of the extracellular matrix to which the cells attach.
Professor Martin Humphries, dean of the faculty of life sciences at the University of Manchester and one of the paper's co-authors, says the study suggests some new capabilities for cells: "This paper identifies a new kind of bond that is strengthened by cyclical applications of force, and which appears to be mediated by complex shape changes in integrin receptors. The findings also shed light on a possible mechanism used by cells to sense extracellular topography and to aggregate information through 'remembering' multiple interaction events."
The cyclic mechanical reinforcement allows force to prolong the lifetimes of bonds, demonstrating a mechanical regulation of receptor-ligand interactions and identifying a molecular mechanism for strengthening cell adhesion through cyclical forces.
"Many cell functions such as differentiation, growth and the expression of particular genes depend on cell interaction with the ligands of the intracellular matrix," said Cheng Zhu, a professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University and the study's corresponding author. "The cells respond to their environment, which includes many mechanical aspects. This study has extended our understanding of how connections are made and how mechanical forces regulate interactions."
The research was published online by the journal on February 14th. The work was supported by the National Institutes of Health (NIH) and the Wellcome Trust.
Cells of the body regulate adhesion in response to both internally- and externally-applied forces. This is particularly important to adhesion mediated by proteins such as integrins that connect the extracellular matrix to the cytoskeleton – and provide cells with both mechanical anchorages and the means to initiate signaling.
Using delicate force measuring equipment, researchers in Zhu's lab and the laboratory of Andres Garcia – a professor in the Woodruff School of Mechanical Engineering at Georgia Tech – collaborated to study adhesion between integrin and fibronectin, a protein component of the extracellular matrix. What they found was that cyclic forces applied to the bond switch it from a short lived state – with lifetimes of about one second – to a long-lived state that can exist for more than a hundred seconds.
"Force can be very important in biology," said Zhu. "Force has direction, magnitude and duration, so in describing its effects on biological systems, you have to use a more complete language."
Zhu, Garcia and Georgia Tech graduate students Fang Kong, William Parks and David Dumbauld – along with postdoctoral fellow Zenhai Li – used two different mechanical techniques to study the strength of bonds between integrin and fibronectin. One technique measured the bond strengths in purified molecules, while the other studied the effects of them in their native cellular environment.
"We have very precise force transducers that allow us to measure force on the scale of pico-newtons," said Zhu. "We prepare the samples in such a way that we engage only one bond, then we control the application of force and observe what happens."
The researchers first used an atomic force microscope to bring the integrin molecule together with the fibronectin, then separate the two. Instruments measured the pico-newton forces required to separate the molecules, and found that the duration of the bonds increased with the repetition of the contacts.
The second technique, known as BFP, involved the use of a fibronectin-bearing glass bead attached to a red blood cell aspirated by a micropipette. Integrin expressed on the micropipette-aspirated cell was pressed into the bead, then pulled away over repeated cycles. Lifetime measurement confirmed that repeated pulling increased the longevity of the bonds.
The researchers studied two integrins, part of a family of 24 related molecules that operate in humans. In future work, they hope to determine whether or not the cyclic mechanical reinforcement they observed is a universal property of many cellular adhesion molecules.
The researchers also hope to explore how cells use this cyclic mechanical reinforcement. Because many disease processes result from abnormal cellular adhesion mechanisms, a better understanding could provide insights into how cardiovascular disease, cancer and immune system disorders operate.
"The findings of the paper have deep implications for our understanding of force-regulated signaling," added Humphries. "There is abundant biological evidence for profound effects of extracellular tensility and elasticity in controlling processes such as cancer cell proliferation and stem cell differentiation, but the mechanisms whereby this information is transduced across the outer cell membrane are unclear."
Journal reference: Molecular Cell
Provided by Georgia Institute of Technology
- Scientists identify how cells respond to mechanical force Jul 08, 2011 | not rated yet | 0
- Research yields potential target for cancer, wound healing and fibrosis Mar 18, 2009 | not rated yet | 0
- Gauging the forces between cells Jul 19, 2012 | not rated yet | 0
- Researchers find three unique cell-to-cell bonds Nov 01, 2012 | not rated yet | 0
- New finding in cell migration may be key to preventing clots, cancer spread Jan 14, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
1 hour ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
Medical research 16 hours ago | 5 / 5 (2) | 0 |
Discovery of circadian clock in mice hair reveals period of time when damage from radiotherapy can be quickly repaired
Discovering that mouse hair has a circadian clock - a 24-hour cycle of growth followed by restorative repair - researchers suspect that hair loss in humans from toxic cancer radiotherapy and chemotherapy ...
Medical research 16 hours ago | 5 / 5 (2) | 1 |
Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...
Medical research 17 hours ago | 4.9 / 5 (7) | 3 |
New research from the University of Southampton has shown that blind and visually impaired people have the potential to use echolocation, similar to that used by bats and dolphins, to determine the location of an object.
Medical research 20 hours ago | not rated yet | 1 |
A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...
Medical research 20 hours ago | not rated yet | 0
(HealthDay)—Injections of a sugar solution appear to help relieve knee pain and stiffness related to osteoarthritis, a new study suggests.
53 minutes ago | not rated yet | 0 |
(Medical Xpress)—Scientists at the School of Medicine have shown that their previously identified therapeutic approach to fight cancer via immune cells called macrophages also prompts the disease-fighting killer T cells ...
1 hour ago | not rated yet | 0 |
Over the past few decades, scientists have developed many devices that can reopen clogged arteries, including angioplasty balloons and metallic stents. While generally effective, each of these treatments ...
56 minutes ago | not rated yet | 0 |
(HealthDay)—Obese and overweight men and women who suffer from heartburn often report relief when they lose weight, a new study shows.
43 minutes ago | not rated yet | 0 |
(HealthDay)—When it comes to the care of your children's teeth, dentists aren't the only experts who can help.
1 hour ago | not rated yet | 0
(Medical Xpress)—In a recent subgroup analysis of the largest blood pressure treatment trial in history, University of Alabama at Birmingham (UAB) researchers found that women and men react the same to ...
17 minutes ago | not rated yet | 0