“Reporter molecules” report from the cell interior
Multifunctional synthetic molecules introduced into living cells

Ulm University

Scientists from Ulm and Mainz have produced “customised”, multifunctional synthetic molecules that can be introduced into living cells. With fluorescence microscopy, the researchers can track the self-organisation of the molecules and draw conclusions about mechanisms in the cell interior. Their article was published in the renowned journal “Nature Communications”.

Chemists and toxicologists at Ulm University and the Max Planck Institute for Polymer Research in Mainz modified thiophene-based oligomers in such a way that they can be introduced into living cells. “We have a lot of experience in producing synthetic molecules, but so far their numerous properties as materials have only been tested in labs and not under physiological conditions. The customised molecules are equipped with groups, which allow them to be dissolved in a non-aqueous environment. The fine tuning of individual structural components allows the new molecules to also be detected optically,” explains Professor Ulrich Ziener from the Institute of Organic Chemistry III at Ulm University.

With these properties, the scientists can even track the self-organisation of the “designer molecules” in the cell: “With fluorescence microscopy, we see if the molecules appear individually or in compounds. It is also possible to observe where and at what time the self-organisation occurs,” Ziener continues. The only challenge is localising the molecules in the fluorescent cells.

Clues to processes in the cell interior

The modified oligomers have an overall “reporter function”. They help scientists to understand mechanisms in the cell interior. In the course of the study, the researchers interrupted intra-cellular transport pathways and traced the altered molecular movements.
The molecules move across various cell compartments, depending on their exact structure, into the vicinity of the cell nucleus and form large molecular compounds there – or they accumulate in the mitochondria, i.e. the cell power plants. This can be controlled via the use of a specific pharmacological inhibitor and lowering the temperature: “In the long term, detailed knowledge about these processes in the cell interior could lead to the deliberate use of drugs that attack mitochondria, for example,” says Professor Holger Barth from the Institute of Pharmacology and Toxicology at the Ulm University Hospital. Further research is still necessary on the exact localisation of the molecules inside the cell, however. But even now, the synthetic molecules are already providing researchers with unexpected insights into the cell interior.

Prof Ulrich Ziener researches at the Institute of Organic Chemistry III at Ulm University. (Photo: Eberhardt/Uni Ulm)
Controlled intra-cellular self-organisation of molecules: synthetic oligomers are absorbed into the cell with the aid of a complex with human albumin (HSA). Fluorescence can be used to distinguish in real time between the molecularly dissolved (green) and aggregated state (red). Dependent on the molecular structure, different cell compartments such as endosomes, mitochondria and structures close to the cell nucleus can be controlled. (Image: Institute of Organic Chemistry III)