What does a cell eat? This new tool makes it visible
What if you could watch a single cell eat in real time? This could answer questions about diseases such as cancer. PhD candidate Yixuan Wang has developed a glowing chemical tool that makes this possible, revealing how living cells take in nutrients.
To understand how cells take up nutrients, researchers long had to break open millions of cells at once. “That only gives you an average picture, not what is happening inside a single living cell,” says PhD candidate Yixuan Wang. “You miss what happens at the individual level, while that is exactly what matters for research into health and disease.”
To solve this problem, the team developed a chemical tool that starts to glow as soon as a cell takes up nutrients. The method works in living cells without disturbing their normal processes.
‘When the nutrient reaches the probe, they react and the fluorescence turns on’
How the glowing system works
The idea is simple: researchers place a “dark” chemical probe inside a specific part of a cell, such as the mitochondria (the cell’s energy source) or the nucleus (its control center). This probe stays invisible until a nutrient enters the cell. ‘When the nutrient reaches the probe, they react and the fluorescence turns on,’ says Wang.
The key to this reaction is a chemical compound called tetrazine. It stays dark until it reacts, then lights up instantly. The approach is based on so-called click chemistry, a Nobel Prize–winning concept.
‘Click chemistry is an approach in which very small chemical groups are incorporated into molecules and made to react in a highly selective way,’ explains supervisor Sander van Kasteren. ‘This allows us to track molecules in living systems without attaching large glowing molecules. We hope to learn, for example, which cells in a tumor consume which nutrients and whether this affects tumor aggressiveness.’
What the researchers discovered
The team studied sugars, fats, and amino acids. They found that some cells, like activated T cells, are extremely active in nutrient uptake, taking up everything for growth and development. In addition, nutrients often ended up in mitochondria. ‘That was unexpected,’ Wang says. ‘It shows how important energy production is during nutrient use.’
Why this matters for disease
The way cells handle nutrients is closely linked to diseases such as cancer. ‘If we know which nutrients tumor cells prefer, we can try to block their uptake,’ Wang explains. This provides an excellent monitoring tool: ‘If we are going to develop a new drug to 'starve' cancer cells by cutting off their food chain, we can now finally use our own eyes to clearly see whether these cancer cells are actually starving.’
In the future, the tool could also be used in diagnostics, for example to detect tumor cells based on their nutrient use,
A platform for future research
Unlike other methods, this technique shows not just where nutrients end up, but how they move over time. ‘Our method detects nutrients as soon as they enter the cell,’ says Wang. In the future, the tool could also be used in diagnostics, for example to detect tumor cells based on their nutrient use. Ultimately, Wang hopes, the method could find applications in industry, for example in developing new drug molecules.
Challenges and personal moments
Developing the tool was challenging. Choosing the right chemical reaction and designing the probe took time. ‘After several failures, I almost gave up,’ Wang recalls. ‘But my supervisor encouraged me to continue.’ That support paid off. When the research was finally published, it was a moment to celebrate.
Wang hopes the work will inspire others. ‘I hope people can build on this idea and develop new tools,’ he says.
By making the invisible visible, this glowing tool offers a new window into the hidden life of cells – and how disease begins.
PhD defence
Yixuan Wang defended his thesis ‘Tools for real-time study of bioorthogonal conversions in the living system’ on 25 March in the Academic building. His promoters are Professor Sander van Kasteren and Professor Hermen Overkleeft.