Certain bonds connecting biological cells get stronger when they’re tugged.
Those bonds could help keep hearts together and pumping; breakdowns of those bonds could help cancer cells break away and spread.
This ribbon diagram shows a pulling force applied to two common adhesion proteins called cadherins (red and blue) bound together in an X-shape. The green spheres represent calcium ions while the cyan and orange stick figures correspond to amino acids brought together as the force is applied. The hydrogen bonds that form between the amino acids create catch bonds that get stronger when pulled. Larger image. Image courtesy of Sanjeevi Sivasankar
Those bonds are known as catch bonds and they’re formed by common adhesion proteins called cadherins. Sanjeevi Sivasankar, an Iowa State University assistant professor of physics and astronomy and an associate of the U.S. Department of Energy’s Ames Laboratory, has described catch bonds as “nanoscale seatbelts. They become stronger when pulled.”
But how does that happen? How can bonds get stronger under force? Sivasankar and his research team have found long-lived, force-induced hydrogen bonds are the answer. A paper describing their findings, “Resolving the molecular mechanism of cadherin catch bond formation,” has just been published online by Nature Communications. Sivasankar is the corresponding author.
Co-authors are Kristine Manibog, an Iowa State graduate student in physics and astronomy and a student associate of the Ames Laboratory; Hui Li, of the Suzhou Institute of Biomedical Engineering and Technology of the Chinese Academy of Sciences in Suzhou New District, China; and Sabyasachi Rakshit, of the Indian Institute of Science Education and Research in Mohali, India. Li and Rakshit are former postdoctoral researchers in Sivasankar’s laboratory.
The team’s research was supported by grants from the American Cancer Society and the American Heart Association. Sivasankar said strong cell-to-cell bonds are important to heart health and fighting cancer. He said the bonds connecting heart cells have to withstand constant mechanical forces. And, in some cancers, he said bonds no longer resist forces, allowing cancer cells to detach and spread.
To find the mechanism behind the strong ties created by catch bonds, Sivasankar’s research team began with molecular dynamics and steered molecular dynamics computer simulations based on data from previous experiments. They found that two rod-shaped cadherins bound together in an X-shape (called an X-dimer) form catch bonds when pulled and in the presence of calcium ions.
The calcium ions keep the cadherins rigid and ordered while the pulling brings parts of the proteins closer together. All of that allows a series of hydrogen bonds to form. These long-lived, force-induced hydrogen bonds lock the X-dimers into tighter contact. Sivasankar said the researchers followed up the simulations with single-molecule experiments using atomic force microscopy.
The experiments confirmed that cadherin X-dimers, when pulled and exposed to high calcium ion concentrations, formed catch bonds. Take away the force or the calcium ions, and catch bond formation was eliminated.
All of this, Sivasankar said, helps explain the biophysics of cell-to-cell adhesion. And that’s important to all of us. “Robust cadherin adhesion,” the researchers wrote in their paper, “is essential for maintaining the integrity of tissue such as the skin, blood vessels, cartilage and muscle that are exposed to continuous mechanical assault.”
Sanjeevi Sivasankar | Eurek Alert!
Rochester scientists discover gene controlling genetic recombination rates
23.04.2018 | University of Rochester
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
23.04.2018 | Physics and Astronomy
23.04.2018 | Physics and Astronomy
23.04.2018 | Trade Fair News