Researchers at Karolinska Institutet in Sweden have headed a study that provides new knowledge about the EphA2 receptor, which is significant in several forms of cancer.
This is important knowledge in itself – but just as important is how this study, which is published in the highly respected journal Nature Methods, was conducted. The researchers used the method of DNA origami, in which a DNA molecule is shaped into a nanostructure, and used these structures to test theories about cell signalling.
DNA-origami graphics. Credit: Björn Högberg
It was previously known that the EphA2 receptor played a part in several forms of cancer, such as breast cancer. The ligand, i.e., the protein that communicates with the receptor, is known as an ephrin molecule. Researchers have had a hypothesis that the distance between different ligands – in this case the distance between ephrin molecules – affects the level of activity in the communicating receptor of the adjacent cells.
The Swedish researchers set out to test this hypothesis. They used DNA building blocks to form a stable rod. This has then been used as a very accurate measure of the distance between molecules.
“We use DNA as the construction material for a tool that we can experiment with”, says Björn Högberg, principal investigator at the Department of Neuroscience. “The genetic code of the DNA in these structures is less important in this case.”
The researchers attached proteins, or ephrins, to the DNA rod at various intervals, for example 40 or 100 nanometres apart. The DNA rods were then placed in a solution containing breast cancer cells. In the next step, the researchers looked at how active EphA2 was in these cancer cells.
It turned out that if the ephrin molecules were placed close together on the DNA rod, the receptor in question became more active in the cancer cells, and the cells also became less invasive in respect of the surrounding cells, which could be an indication that they became less prone to metastasis. This was true even though the amount of protein was the same throughout the experiments, i.e., the number of attached molecules remained the same.
“For the very first time, we have been able to prove this hypothesis: the activity of EphA2 is influenced by how closely spaced the ligands are on the surrounding cells”, says Björn Högberg. “This is an important result in itself, but the point of our study is also that we have developed a method for examining how cells react to nearby cells in a controlled environment, using our custom DNA nano-calipers.”
The researchers describe the cell communication as a form of Braille, where the cells somehow sense the protein patterns of nearby cells, and where the important thing is not only the amount of proteins, but to a great extent the distance between them as well. This study found that a cluster of proteins would communicate more actively than sparsely spaced proteins, even if the concentration was the same.
“This is a model that can help us learn more about the importance of the spatial organization of proteins in the cell membrane to how cells communicate with each other, something that will hopefully pave the way for a brand new approach to pharmaceuticals in the long term”, says Ana Teixeira, a principal investigator at the Department of Cell and Molecular Biology.
“Today, the function of the pharmaceuticals is often to completely block proteins or receptors, but it is possible that we should rather look at the proteins in their biological context, where the clustering and placement of various proteins are relevant factors for the effect of a drug. This is probably an area where there is important knowledge to obtain, and this is a way of doing it.”
The study is financed by funds from the Swedish Research Council, the Strategic Research Program in Stem Cell Research and Regenerative Medicine (StratRegen) at Karolinska Institutet, Vinnova, Carl Bennet AB.
Katarina Sternudd | AlphaGalileo
New method opens crystal clear views of biomolecules
11.02.2016 | Deutsches Elektronen-Synchrotron DESY
Scientists from MIPT gain insights into 'forbidden' chemistry
11.02.2016 | Moscow Institute of Physics and Technology
Today, plants and microorganisms are heavily used for the production of medicinal products. The production of biopharmaceuticals in plants, also referred to as “Molecular Pharming”, represents a continuously growing field of plant biotechnology. Preferred host organisms include yeast and crop plants, such as maize and potato – plants with high demands. With the help of a special algal strain, the research team of Prof. Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam strives to develop a more efficient and resource-saving system for the production of medicines and vaccines. They tested its practicality by synthesizing a component of a potential AIDS vaccine.
The use of plants and microorganisms to produce pharmaceuticals is nothing new. In 1982, bacteria were genetically modified to produce human insulin, a drug...
Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".
Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...
The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.
Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...
Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.
The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).
Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels
A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...
09.02.2016 | Event News
02.02.2016 | Event News
26.01.2016 | Event News
11.02.2016 | Life Sciences
11.02.2016 | Physics and Astronomy
11.02.2016 | Earth Sciences