Cancer cells are an example of how cells can be exposed not only to (bio)chemical stimuli, but also to physical ones. On the one hand, there is the chemical composition of the tumor environment, including a complex cocktail of endogenous signaling molecules as well as xenobiotics (e.g. drugs). On top of this, there are the physical forces that arise as the tumor mass grows or during the metastatic process. Molecular mechanisms that enable cells to deal with both aspects are a central theme of our research. 

There's the question of how the two pilots work together and whether one pilot can take over if the other fails.

"To draw a simplified parallel with daily life, we could compare it to the work of two pilots, both can control an airplane, namely the cell. One pilot is the chemical stimulation, the other is the physical," says Giorgia Del Favero of the Institute of Food Chemistry and Toxicology. Beyond that, there's the question of how the two pilots work together and whether one pilot can take over if the other fails. In an interview, the toxicologist talks about her research and challenges.

What is behind your research focus on "biophysical toxicology"?

We now know that cells react to both chemical and physical stimulation and modulate in this way complex pathophysiological processes. On contact with chemicals, such as active or toxic substances, cells typically react according to the "dose-response principle", namely the higher the dose, the greater the effect. We take this classical toxicological principle and develop it further, considering physical cues that can potentially influence these responses. In addition, we want to clarify how chemical substances can influence cell motility, and we are looking for ways to integrate physiological forces in cell cultures.

Let us think to the intestine, where physical stimuli are particularly pronounced due to the necessary organ contraction that allows the passage of the food chyme. Here we have already shown that some food components or contaminants can alter the biomechanical response capacity of intestinal cells. On the other hand, we are now trying to understand how physical stimuli can possibly contribute to the physiological function of intestinal cells and thus influence the response to nutrients or food toxins.

In an FWF project, you are investigating the development of ovarian cancer cells. What role does movement play here?

In this project, we want to understand if physical stimuli could contribute to the development of particularly aggressive forms of cancer, namely in ovarian cancer. Therefore, our central hypothesis is that the aggressiveness of ovarian cancer can be traced back to the particular biophysical environment in the peritoneal cavity, which is characterized by high motility. We hope that our findings will ultimately favor the development of new therapeutic approaches and more efficient chemotherapy.

In toxicology today, one often speaks of a paradigm shift. In what way?

Many classical approaches in toxicology are based on animal experiments. Today, research moves toward alternative methods, e.g. in silico screenings or in vitro cell models, that should help to reduce or ideally completely replace animal-based tests. We are also committed to give our contribution here, supporting the development of new efficient approaches that can be used for toxicological evaluation, for instance with models that also include movement and cell motility as central factors. Obviously, the quality and predictive power of the data should always stay in the foreground and the ultimate goal here is to generate highly predictive data for human toxicology.  

What is a central message that you pass on to students in your teaching?

Not for everybody is immediately clear what toxicology has to do with chemistry. However, it is enough to think to the topic of risk assessment of chemicals and the connection becomes straightforward. In fact, risk assessment including toxicological analyses is a fundament for the EU chemicals regulation REACH. Chemistry and toxicology are complementary tools to define the handling of known chemicals as well as for the characterization of newly developed substances. Thus, in the new course on chemical law and safety in the master's program in chemistry, I try to introduce these concepts to our students.

In addition, toxicology can help answer many different questions, e.g., related to food safety, research on nanomaterials, environmental protection, or drug development. These topics are of central importance to me in both research and teaching.

Ass.-Prof. Giorgia Del Favero leads the group "Biophysical Toxicology" at the Institute of Food Chemistry and Toxicology and has already been head of the Core Facility Multimodal Imaging since 2019. Since July 2022, she is also a tenure track professor for "Toxicology". In her research, she investigates chemical-physical factors that contribute to cellular pathophysiological adaptation (e.g. in intestinal, bladder or ovarian cancer cells). https://biophysical-toxicology.univie.ac.at/

• Jobst M., Kiss E., Gerner Ch., Marko D., Del Favero G., Activation of autophagy triggers mitochondrial loss and changes acetylation profile relevant for mechanotransduction in bladder cancer cells, Archives of Toxicology, 2023 Jan;97(1):217-233. doi: 10.1007/s00204-022-03375-2.
• Rebhahn V.I.Ch., Kiss E., Marko D., Del Favero G., Foodborne compounds that alter plasma membrane architecture can modify the response of intestinal cells to shear stress in vitro, Toxicology and Applied Pharmacology, Volume 446, 1 July 2022, DOI: 10.1016/j.taap.2022.116034