Revolutionizing Magnesium Detection & The Metal Balance Within Us

Apr 27

By Maia Vierengel

Dr. Daniela Buccella, PhD

When we think about metals in our body, we shudder and think about toxic metals leaching from lead paints or faulty takeout containers. But to Daniela Buccella, Professor in the Department of Chemistry at Emory University, the idea of metals in the body is completely normal; in fact, our bodies need many different types of metals to function optimally.

The way metals such as magnesium, calcium, and iron behave inside our cells is still a mystery, despite being vital to many biological functions. This is largely due to challenges in sensing these metals in a complex mixture. Chemically, metal ions with the same charge look and behave very similarly. For example, calcium and magnesium have been near-impossible to distinguish with traditional tools for decades.

That’s why Buccella has dedicated her research efforts to designing novel molecular probes to detect and measure metal ions in live cells. In one of her most recent publications, her team designed a small-molecule chemical probe to specifically measure magnesium, or Mg2+, in live cells. When the Mg2+ ion binds the probe, called MagZet1, it changes its chemical conformation, resulting in a color change from green to blue.

The detection of magnesium has serious implications for disease diagnostics. Abnormal levels of this metal have been associated with many conditions, including cardiovascular disease, metabolic dysregulation, cancer, and liver disorders. Acetaminophen, an over-the-counter painkiller, is responsible for 50% of overdose-related acute liver failure. So, when Buccella’s collaborators reached out with a question of how acetaminophen would affect magnesium levels in liver cells, she had the perfect tool to answer it.

Buccella and her team found that Mg2+ levels decrease even within 1 hour of dosing with acetaminophen using MagZet1. Given that it was unknown whether magnesium levels were affected at all by this drug, this is a major finding. The team also demonstrated that MagZet1 is very robust and allows for high-throughput sensing of magnesium in cells, which Daniela says may indicate major therapeutic potential. “I think what we are generating at this time – our research tools – I don't discount eventually being able to use them for diagnostics.”

Different forms of magnesium are gaining serious popularity as dietary supplements, with consumers observing health benefits such as reduced blood pressure and improved sleep. However, we still have a limited understanding of magnesium’s role in these processes, and how the balance of magnesium with other metals results in these health outcomes.

Buccella emphasizes the importance of specificity when it comes to detecting the different metal ions. Magnesium and calcium are chemically very similar, but play distinct functions in our bodies. “I think a lot of the issues people have had with the magnesium balance and why magnesium supplements are kind of working is because people have been taking calcium for a long time,” says Buccella, “Calcium displaces magnesium. And so, the key is really getting the right ratio of the two, not just one or the other.”

This yin-yang relationship between these two near-identical metals is one of many blind spots when it comes to our understanding of metal interactions in biology. To shed more light on their relationship, scientists in different disciplines will need to work together to develop new metal detection tools.

MagZet1 is a major advancement for metal ion detection, and mainly possible because of collaborative research. While Buccella initially steered clear of health-related research, she realized that expertise in inorganic chemistry was vital to answering questions about metal ions in biology. “We [scientists] are becoming a lot more adapted doing these kinds of interdisciplinary studies and working together”, says Buccella. “I mean, I never thought that I would be working with a liver biologist, but we could find common ground when we look at things on a molecular level.”

Work from teams like Buccella’s and her collaborators can lead to the advent of the metallome, or the complete mapping of metals in our cells. For instance, MagZet1 now allows us to study the role of magnesium deficiency in liver disorders. Strides are also being made in the development of biological sensors for zinc, copper, and iron. Further studies will allow scientists to be able to piece together the role of these imperative ions in cancers, neurodegenerative diseases, and metabolic health.

Metal activity in our bodies and their link to diseases have remained an enigma for decades. As we look toward the future, we should embrace the balance of metals within us to live our best lives.