For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of the Swiss Nanoscience Institute and the NCCR “Molecular Systems Engineering”, the group led by Professor Cornelia Palivan from the Department of Chemistry at the University of Basel is working to produce organelles of this kind in the laboratory, to introduce them into cells, and to control their activity in response to the presence of external factors (e.g. change in pH values or reductive conditions).
These cellular implants could, for example, carry enzymes able to convert a pharmaceutical ingredient into the active substance and release it “on demand” under specific conditions. Administering drugs in this way could considerably reduce both the amounts used and the side effects. It would allow treatment to be delivered only when required by changes associated with pathological conditions (e.g., a tumor).
Tiny capsules with an enzymatic cargo
The artificial organelles are based on tiny capsules that form spontaneously in solution from polymers and can enclose various macromolecules such as enzymes. The artificial organelles presented here contained a peroxidase enzyme that only begins to act when specific molecules penetrate the wall of the capsules and support the enzymatic reaction.
To control the passage of substances, the researchers incorporated chemically modified natural membrane proteins into the wall of the capsules. These act as gates that open according to the glutathione concentration in the cell.
At a low glutathione value, the pore of the membrane proteins are “closed” – that is, no substances can pass. If the glutathione concentration rises above a certain threshold, the protein gate opens and substances from outside can pass through the pore into the cavity of the capsule. There, they are converted by the enzyme inside and the product of the reaction can leave the capsule through the open gate.
Also effective in living organisms
In collaboration with the group led by Professor Jörg Huwyler of the Department of Pharmaceutical Sciences at the University of Basel, the artificial organelles have also been studied in vivo. “We’ve now been able to integrate these controllable artificial organelles into the cells of a living organism for the first time,” says Cornelia Palivan.
The researchers chose zebrafish embryos because their transparent bodies allow excellent tracking of the cellular implants under a microscope when they are marked with a fluorescent dye.
After the artificial organelles were injected, they were “eaten” by macrophages and therefore made their way into the organism. The researchers were then able to show that the peroxidase enzyme trapped inside the artificial organelle was activated when hydrogen peroxide produced by the macrophages entered through the protein gates.
“In this study, we showed that the artificial organelles, which are inspired by nature, continue to work as intended in the living organism, and that the protein gate we incorporated not only works in cell cultures but also in vivo,” comments Tomaž Einfalt, the first author of the article and graduate of the PhD School of the Swiss Nanoscience Institute. The idea of using artificial organelles as cell implants with the potential to produce active pharmaceutical compounds, for example, opens up new perspectives for patient-oriented protein therapy.
T. Einfalt, D. Witzigmann, C. Edlinger, S. Sieber, R. Goers, A. Najer, M. Spulber, O. Fischer, J. Huwyler, and C. G. Palivan
Biomimetic artificial organelles with in vitro and in vivo activity triggered by reduction in microenvironment
Nature Communications (2018), doi: 10.1038/s41467-018-03560-x
Prof. Dr. Cornelia G. Palivan, University of Basel, Department of Chemistry, tel. +41 61 207 38 39, email: email@example.com
Prof. Dr. Jörg Huwyler, University of Basel, Department of Pharmaceutical Sciences, tel. +41 61 207 15 13, email: firstname.lastname@example.org
Reto Caluori | Universität Basel
Investigating cell membranes: researchers develop a substance mimicking a vital membrane component
25.05.2018 | Westfälische Wilhelms-Universität Münster
New approach: Researchers succeed in directly labelling and detecting an important RNA modification
30.04.2018 | Westfälische Wilhelms-Universität Münster
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences