At Tampere University, researchers develop new tools for the optical control of cells. These tools are handy for understanding processes where a fast initial signal initiates long-term cell or tissue function changes.
Challenges in Optical Control of Cells
Using light to control biological functions has opened new opportunities in various fields, particularly neurosciences. Light enables tightly controlled activation in a specific location and allows regulation at different scales, ranging from individual cells to whole organisms. On the molecular level, light-activated control is usually achieved through modified proteins that react to a specific wavelength of light.
With the current tools, however, the effects appear slowly, and continuous light activation is needed for sustained results. This limits the applicability of the methods in the control of fast processes, leading to unwanted toxicity in the studied cells or organisms.
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Overcoming the Limitations of Light-Activated Control
Researchers at Tampere University collaborated with experts from the University of Cambridge and the University of Pittsburgh to explore ways to overcome the limitations of existing tools for the optical control of cells. The team aimed to achieve fast and cell-friendly control of irreversible protein binding by building on their previous expertise on proteins that form irreversible bonds.
To make this possible, the experts used their previously developed "protein superglue," a SpyTag003/SpyCatcher003 peptide/protein pair that exhibits fast irreversible binding. Based on an engineered Streptococcus pyogenes protein, the SpyTag003/SpyCatcher003 peptide/protein pair enables a Lego brick-like modular assembly of complex protein structures.
To achieve their goal, the researchers also had to reach beyond the 20 amino acids that constitute human proteins. They incorporated a light-reactive unnatural amino acid into the SpyCatcher003 protein using archaebacteria's modified protein synthesis machinery. They strategically placed the synthetic amino acid to block the peptide/protein pairing until its activation by exposure to light.
According to Professor Mark Howarth, a short pulse of light was enough to trigger the rapid and efficient formation of the irreversible peptide/protein complex in living cells and the test tube. The activation also took place with specific wavelengths of light, which makes it possible to combine protein control with live-cell fluorescence microscopy.
Human cells attach to the surrounding tissue through cell adhesions or large protein complexes made of hundreds of different proteins. The research team split a central adhesion protein called talin into two halves. It explored their newly developed tools for the light-activation of talin protein inside living cells.
The tight control over adhesion formation enabled the scientists to explore the earliest events in the formation of cell adhesions. The researchers determined a timeline of events in adhesion complex formation by tracking the timing of protein recruitment into the adhesion complex.
The research findings demonstrated the potential of the light-activated protein superglue for studying complex cellular processes. They also pave the way for a comprehensive understanding of adhesion's complex structure and function.
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