A strong and highly selective instant adhesive inspired by the bacterium Streptococcus pyogenes has been developed by Oxford University researchers. S. pyogenes is a common resident of human throats that is normally kept in check by the body's defenses, but when it gets out of control it can cause diseases ranging from strep throat to toxic shock syndrome or flesh-eating disease. By engineering a protein that is central to S. pyogenes' infectious arsenal, the researchers have developed a new superglue that can't be matched for sticking molecules together and not letting go.

S. pyogenes have thin protein hairs which extend from the bacterium to form strong attachments to human cells. The 3D structure of a protein, wherein the long chains of amino acid polymers are folded and looped up into three-dimensional structures, are usually the result of relatively weak hydrophobic interactions and hydrogen bonding.

S. pyogenes FbaB protein in its 3D structure (Image: National Center for Biotechnology Information)

However, a special protein called FbaB found in S. pyogenes has a 3D structure that is stabilized by formation of an extremely strong intramolecular isopeptide bond. This isopeptide bond is not broken by boiling in detergent or strong acids. In fact, using an atomic force microscope (AFM), the isopeptide bond was found to survive a force along the protein chain of one nanoNewton, roughly corresponding to the tensile strength of a carbon nanotube. The AFM study did not reveal the strength of the isopeptide bond, as the rest of the protein broke before the isopeptide bond.

Formation of a very strong isopeptide chemical bond between a lysine and an aspartic group on the same CnaB2 adhesin region (Image: Oxford University)

The Oxford team formed a new protein, which shares the isopeptide bond, but is much smaller and simpler in structure than FbaB. They found a way to split the protein at the isopeptide bond, giving a protein and a peptide each of which possesses one of the spontaneously active groups of this enormously strong bond. The protein and peptide are separated and incorporated into a two-part adhesive carrier.

With this new approach the protein and peptide partners are easy to produce and react irreversibly through formation of an amide bond, simply upon mixing. The two parts are permanently locked together, just as the original FbaB protein was locked permanently into a particular 3D structure. This lock is stable over time, high temperatures, high forces and with harsh chemical treatment.

The team have given the bonding fragments the moniker "SpyCatcher" and "SpyTag" for the larger and smaller fragments respectively. In biochemical research S. pyogenes is unimaginatively abbreviated "Spy," and a tag is a peptide sequence genetically attached to a recombinant protein. SpyCatcher was named because once SpyCatcher gets hold of the shorter protein segment, SpyTag, it never lets go.

When SpyCatcher and SpyTag are brought together, they bond in minutes with high yield (over 80 percent). It doesn't matter whether it is in acidic or neutral conditions, or whether it is 4°C (39°F) or 37°C (99°F). An important attribute for one of the world's strongest adhesives is that SpyCatcher and SpyTag won't bond to fingers - they will only stick to each other. Being the basis of an adhesive, however, the adhesive carriers will have to bond to other materials, as SpyTag and SpyCatcher cannot.

Further development of the new class of adhesives is ongoing through the auspices of Isis Innovation, Oxford University's technology transfer arm.

Source: Oxford University