Researchers develop light-activated protein superglue for fast and precise control of cells and tissues

Researchers at Tampere University have been involved in an international study to develop new tools for the light-activated control of cells. These tools are especially welcome for understanding processes where a fast initial signal leads to long-term changes in cell or tissue function. The modular Lego brick-like structure makes the tools widely applicable in the study of diverse cellular functions.

As a starting point, the team used their previously developed "protein superglue," a SpyTag003/SpyCatcher003 peptide/protein pair exhibiting an extremely fast irreversible binding. Based on an engineered Streptococcus pyogenes protein, the SpyTag003/SpyCatcher003 peptide/protein pair allows a Lego brick-like modular assembly of complex protein structures.

To achieve their goal – the optical control of protein superglue – the team had to reach beyond the 20 amino acids constituting human proteins. Using a modified protein synthesis machinery from archaebacteria, the team incorporated a light-reactive unnatural amino acid into the SpyCatcher003 protein. The unnatural amino acid was strategically placed to block the peptide/protein pairing, until its activation by exposure to light.

"A short pulse of light was enough to trigger the rapid and efficient formation of the irreversible peptide/protein complex both in the test tube and in living cells," says Professor Mark Howarth, about the performance of the photoactivated SpyCatcher003. "Importantly, the activation only took place with specific wavelengths of light, making it possible to combine protein control with live-cell fluorescence microscopy."

Image source: Protein Dynamics group/Tampere University.