Amino Acids: The Unsung Heroes of Protein Stability

For years, amino acids have played a pivotal role in medical formulations like insulin, acting as stabilizers to prevent unwanted interactions among proteins. While researchers acknowledged their effectiveness, the underlying reasons remained shrouded in mystery—until now.

An international team of scientists, spearheaded by the Supramolecular Nano-Materials and Interfaces Laboratory at EPFL, has unveiled the intriguing mechanics behind this phenomenon, revealing a universal stabilizing effect of small molecules in solution. This groundbreaking research was published in *Nature*, alongside contributions from Alfredo Alexander-Katz at MIT and specialists at the Southern University of Science and Technology in China, including EPFL alum Zhi Luo.

A Shift in Understanding: The Real Role of Amino Acids

Traditionally, it was believed that proteins, when suspended in solution, are molded into various shapes, and amino acids helped maintain their proper folding. However, recent insights from EPFL PhD graduate Ting Mao challenge this notion.

"We discovered that the stabilizing properties of amino acids aren’t just biological responses; they reflect a broader physical property shared by all small molecules interfacing with larger particles, or colloids, in solution," explains Mao.

The Screen Effect: Balancing Interactions Like a Crowded Hallway

To grasp this concept of 'screening attraction', Lab director Francesco Stellacci paints a vivid analogy: two colleagues in a hallway.

"If the hall is empty, they'll easily spot and greet each other. But in a crowded hallway, they might miss each other completely. Amino acids function as this crowd, inhibiting interactions among larger particles—or proteins—much like individuals ignoring one another in a bustling space," he elaborates.

Amino Acids vs. Salts: The Anti-Salt Effect

In contrast, salts are known to 'screen repulsion.' In Stellacci's analogy, salts encourage unfriendly colleagues to interact awkwardly, whereas amino acids discourage favorable interactions, acting as the 'anti-salt.' This effect is even observed in nature, as plants increase amino acid production when exposed to salty waters to counteract stress.

Implications for Future Research and Biomedical Applications

The study emphasizes the importance of accurately reporting amino acid concentrations in scientific research, akin to how ionic strength is reported. "Understanding the impact of these concentrations could revolutionize experimental biology and protein stability assessments," Stellacci asserts.

With a new ERC Advanced Grant, Stellacci aims to explore the vital role of such small molecules in biological systems, ultimately working towards predicting which amino acids best stabilize specific proteins—moving beyond the trial-and-error approach currently used in biomedical research.