Human cells are protecting their proteins from unfolding and aggregating. That's what biophysicist Alireza Mashaghi and his team discovered after seven years of in-depth research into the folding mechanisms of proteins. With an unprecedented approach, the team was able to study the folding of a single protein molecule.
Proteins are fundamental building blocks of life. These complex molecules do most of the work in our cells. To do their job properly, each protein must be folded into a specific structure. And that's where things sometimes go wrong. If proteins somehow unfold, for example, because of disease, they lose their function or lump together. Understanding the mechanisms behind the folding and stability of proteins is therefore crucial for developing potential new treatments.
How does a protein unfolds under stress?
'We wanted to observe how a single protein unfolds when it's experiencing stress in the cellular environment,' explains Barbara Scalvini, one of the researchers. She and her colleagues developed a new approach combining optical tweezers (see box) and circuit topology: a system to determine and classify the shape of proteins.
With this, they studied a protein in a cytosolic solution - a close approximation of the complex cytoplasmic matrix found within living cells. Scalvini: 'This allowed us firstly to explore how the cellular environment influences the unfolding pathway of a protein. And secondly, to evaluate the resulting protein shape.'
Tweezing with beams of light
Optical tweezers serve as actual tweezers, but on a microscopic scale. It consists of a highly focused light beam that uses light to manipulate objects as small as a single atom. The attractive or repulsive forces provided by this beam can hold and move a microscopic particle.
