Anyone who has ever tried to pry a mussel from wood or rock know how stubborn these underwater mollusks are — and their gluey secret has long captivated scientists. For years, researchers have attempted to replicate the extraordinary adhesive and its properties in the lab, targeting some of the eight proteins that mussels secrete and use to coat an organ called a foot that attaches them to surfaces.
Now, using a novel method to arrange molecules, researchers at Northwestern University have created a material that performs even better than the glue they were trying to mimic. Their findings, reported in a paper in the Journal of the American Chemical Society, expand on how these protein-like polymers can be used as a platform to create new materials and therapeutics.
“The polymer could be used as an adhesive in a biomedical context, which means now you could stick it to a specific tissue in the body,” said Nathan Gianneschi, who led the study and is a professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern University. “And keep other molecules nearby in one place, which would be useful in wound healing or repair.”
Proteins like those secreted by mussel feet exist throughout nature. Evolution has made a habit of creating these long, linear chains of amino acids that repeat over and over (called tandem repeat proteins, or TRPs). Appearing at times stretchy, strong and sticky, these protein frameworks show up in insect wings and legs, spider silk and mussel feet. Scientists know the exact primary sequences of the amino acids that make up many of these proteins, yet have trouble replicating the complicated natural process while still maintaining their extraordinary qualities.
The paper’s first author Or Berger, a postdoctoral researcher in Gianneschi’s lab who studies peptides – short chains of amino acids – came up with an idea for how to arrange amino acid building blocks differently to replicate the properties of the mussel proteins, rather than directly copy their structure.
By taking the building block of one of the proteins (the repeat decapeptide, a 10-amino acid sequence that makes up the mussel foot protein), and plugging it into synthetic polymer, Berger thought the properties may be enhanced.
As associate director of the International Institute for Nanotechnology, Gianneschi has built much of his lab around the idea of using polymer chemistry to mimic the function of proteins. For example, drug therapies like antibodies and other small molecules can combat some diseases, with a nanocarrier used to deliver the drug to its target more effectively. But Gianneschi says that replicating proteins could offer a different approach to biological problems, by changing interactions inside and between cells that are involved in the progression of disease, or between cells, tissues and materials.
“Proteins arrange amino acids as chains, but instead we took them and arranged them in parallel, on a dense synthetic polymer backbone,” Gianneschi explained. “This was the same thing we have begun to do for controlling specific biological interactions, so the same platform technology we will use for future therapeutics has really become potentially interesting in materials science.”
The end result was something that looked like a brush of peptides, rather than looping amino acids together in a straight line as a chain. While this novel process may seem like adding an additional step, forming these protein-like polymers (PLPs) actually skips several steps. The researchers form the peptides in a readily available synthesizer and insert them into the tightly packed backbone rather than going through tedious steps of protein expression.
To test the new material’s efficacy, the researchers applied either the polymer material or the native mussel protein to glass plates. They placed cells on the plates and then, after washing them, assessed how many cells were still present, either attached or not, to gauge how well the materials performed. They found that the PLPs formed a cellular superglue, leaving more cells attached then either the native mixture or an untreated plate.
“We actually didn’t mean to improve on the mussel’s properties,” Berger said. “We only meant to mimic it, but when we went and tested it in several different assays, we actually got better properties than the native material in these settings.”
The researchers hope their model can be widely applicable across other proteins that repeat their sequence to gain function, offering a new way to replicate proteins. They hypothesize that such a platform could perform better than their native counterparts because they are denser and scalable. Gianneschi said this is the first of many papers to discuss polymer-based protein mimics, and he is already thinking about applications for future materials.
Resilin, for example, a stretchy protein found in insect legs and wings, could be used to make flexible drones and other robotics. “When you talk about polymers, some people immediately think of plastic bags and bottles,” Gianneschi said. “Instead, these are very functional, advanced precision materials, made accessible.”
This story is adapted from material from Northwestern University, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.
“Proteins arrange amino acids as chains, but instead we took them and arranged them in parallel, on a dense synthetic polymer backbone. This was the same thing we have begun to do for controlling specific biological interactions, so the same platform technology we will use for future therapeutics has really become potentially interesting in materials science.”Nathan Gianneschi, Northwestern University