Billions of years of evolution have yielded a variety of natural materials, like spider silk and gecko pads, with properties that we're only now just attempting to mimic. Inspired by the structure of Titin, a muscle component that's likely to be the largest protein on Earth, researchers have produced a mesh of material with a similar structure that shows excellent elastic properties. Not only is the work itself impressive, but the design principles behind it may help drive the production of custom-designed proteins for specific uses.

The Titin protein itself has some remarkable properties, but its sheer size makes it almost impossible to work with. In a world where proteins that are 300 amino acids long are common, Titin clocks in at about 33,000. Distilled down to atoms, it has the ludicrous chemical formula C 169723 H 270464 N 45688 O 52243 S 912 . Most studies of the protein itself have looked at its behavior in isolated muscle fibers, since isolating the protein or producing it in bacteria is simply impossible. (I wouldn't be surprised if it's physically comparable in size to a bacteria, but I've not found information to confirm that.)

Despite the inconvenience, researchers have found that it's a remarkably elastic protein, and have ascribed that behavior in part to the many repeated subunits that make up the overall protein structure. Many parts of the protein can fold up into globular structures, which are thought to cluster together; stretching the protein simply causes them to temporarily pull apart.

So, the researchers behind the new work simply built a manageable version of Titin. They spliced together a gene that encoded four of these globular regions, separated by spacers from the resilin protein, which (as the name implies) is another resilient, elastic protein. The resilin spacers were chosen because they appear to be very flexible and have little ordered structure under normal conditions.

The resulting protein was small enough to be produced in bacteria. Once purified, the authors tried stretching it out using an atomic force microscope. The result was a very clean pattern of strain. As the initial force was applied, the protein stretched out with little resistance, thanks to the resilin spacers. Once those were fully extended, though, a sawtooth pattern became apparent, as the strain would increase as each of the globular portions of the protein were pulled apart. Once opened up, the strain would actually decrease until the next globular portion began being pulled open.

All told, opening up each cluster allowed the protein to extend by a total of 18nm; releasing the strain allowed the protein to snap back into its native configuration. Dumping urea onto it, which chemically unfolds proteins, eliminated its elastic properties, indicating that they are dependent upon the protein's underlying structure.

Of course, a few dozen nanometers isn't exactly useful, so the authors developed a procedure for creating a mesh from the protein. A single catalyst, when added to a solution of the protein, could chemically crosslink neighboring molecules together (for the technically inclined, the catalyst caused tyrosine residues to dimerize). The resulting materials could handle strains as high as 135 percent before failing, and would quickly snap back to their normal shape when strain was released. In essence, the material acted a bit like a shock absorber, easily stretching a bit before exerting increasing levels of resistance as the strain rises.

That's not the sort of performance that's ready to replace the materials we're already using when elasticity is key. But the authors point out that the protein mesh is completely biodegradable, and unlikely to set off any adverse reactions if used in a medical implant.

But, in the long term, it's the basic approach that might be most significant. The authors started with a design goal—build an elastic substance—and were able to pick a set of protein domains with the appropriate properties, string them together, and get roughly what they intended. It would seem that there's no reason that additional properties, like binding a specific chemical or catalyzing a reaction, couldn't be tacked on in the same way.

In fact, there are a few barriers to arbitrarily extending this work, but they aren't especially serious limits. For one, not every protein structure will be compatible with a given design goal. So, for example, there are probably some useful pieces of protein, like catalytic domains, that simply won't be elastic—if you pull them open, they'll stay open, and you could kiss the catalytic activity goodbye. There are also a variety of useful protein domains that we don't fully understand, or can't be broken up to convenient pieces for use elsewhere.

Still, the raw biological toolkit is staggeringly large, and we've got a fairly good grip on a lot of it. Most of synthetic biology has focused on stringing together new combinations of genes, but the ability to string together new combinations of gene fragments seems equally promising.

Nature, 2010. DOI: 10.1038/nature09024 (About DOIs).