Freiburg researchers engineer cellular adhesion receptors that can be controlled with light
The ability of cells to adhere to each other and to their environment is the basis for multicellular life. Adhesion occurs via diverse receptors at the surface of cells that bind to specific ligands in their surroundings.
Despite the importance of these adhesion receptors, there is a paucity of tools available for precisely controlling their interactions with the environment.
To address this limitation, an interdisciplinary team of scientists from the Freiburg Signalling Research Excellence Clusters BIOSS and CIBSS have engineered an adhesion receptor and a complementary synthetic extracellular environment that can be activated by light.
This system can be adapted to render other receptor–ligand interactions amenable to precise manipulation with light. The scientists have published their new optogenetic system in Communications Biology.
Optogenetics uses light to control proteins and the cellular processes in which they are involved. “This technique has revolutionized the analysis of cellular signalling because it is non-invasive and because it allows precise spatiotemporal control of signalling processes”, says lead author of the study, Prof. Dr. Wilfried Weber.
Optogenetics has been widely used to control processes inside the cells. The authors decided to bring optogenetics into the extracellular realm, specifically to test whether they could control receptor–matrix interactions using light.
The team of researchers, which also included the groups of Prof. Dr. Gerald Radziwill and Prof. Dr. Wolfgang Schamel, focussed their attention on an important class of receptors – called integrins – that facilitate adhesion to extracellular matrix.
“Although integrins have central roles in many normal biological processes, they can also promote growth and spread of cancer and have thus been explored as targets for anti-cancer therapies.” explains first author Julia Baaske. To control integrin-mediated adhesion using light, the scientists first developed an OptoMatrix coated with a light-sensitive plant protein called phytochrome B.
Then they engineered an OptoIntegrin equipped with a phytochrome-interacting factor (PIF6) and expressed this receptor in cancer cells. Phytochrome B is usually found in its inactive form, but when exposed to a specific wavelength of red light it is activated and can be bound by PIF6; when exposed to infrared light it switches back to the inactive form.
“The most exciting experiment was when we first shone red light on the OptoMatrix: the cells expressing OptoIntegrin immediately adhered to the matrix and activated intracellular signalling processes. Then when we used infrared light, they almost completely detached.” explains Baaske. “Essentially, we have developed light-controlled velcro for human cells”.
The system not only allows integrin–matrix interactions to be turned on and off with high temporal precision; it also allows spatial control. Strong adherence of cells expressing OptoIntegrins only occurs at parts of the Optomatrix that have been activated with light. “This system serves as a blueprint for precise spatiotemporal control of other receptor–ligand interactions using light.” says Weber, who is also a member of the Speaker Team of the recently launched CIBSS Excellence Cluster.
“This and other optogenetic and chemical control-of-function technologies that will be developed in CIBSS will give us unprecedented control of and insight into the spatiotemporal dynamics of biological signalling processes.”
Prof. Dr. Wilfried Weber
CIBSS – Centre for Integrative Biological Signalling Studies
Phone: +49 (0)761 / 203 - 97654
Baaske J., Mühlhäuser W.W.D., Yousefi O.S., Zanner S., Radziwill G., Hörner M., Schamel W.W.A., Weber W. (2019): Optogenetic control of integrin–matrix interaction. In: Communications Biology. DOI: 10.1038/s42003-018-0264-7
Rudolf-Werner Dreier | idw - Informationsdienst Wissenschaft
Antibiotic resistances spread faster than so far thought
18.02.2019 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
The Lypla1 Gene Impacts Obesity in a Sex-Specific Manner
18.02.2019 | Deutsches Zentrum für Diabetesforschung
For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.
The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...
Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens
Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...
Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light
When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...
The so-called Abelian sandpile model has been studied by scientists for more than 30 years to better understand a physical phenomenon called self-organized...
Physicists from the University of Basel have developed a new method to examine the elasticity and binding properties of DNA molecules on a surface at extremely low temperatures. With a combination of cryo-force spectroscopy and computer simulations, they were able to show that DNA molecules behave like a chain of small coil springs. The researchers reported their findings in Nature Communications.
DNA is not only a popular research topic because it contains the blueprint for life – it can also be used to produce tiny components for technical applications.
11.02.2019 | Event News
30.01.2019 | Event News
16.01.2019 | Event News
18.02.2019 | Interdisciplinary Research
18.02.2019 | Process Engineering
18.02.2019 | Studies and Analyses