Prying a mussel from rock, wood or anything else is tough. The underwater mollusks have a gluey secret that has fascinated researchers for a long time.
Image Credit: Shutterstock.com/ Formatoriginal
For years, scientists have tried to imitate the amazing adhesive and its properties in the lab, pursuing some of the eight proteins that mussels discharge and use to apply on an organ known as a foot that mussels use to adhere to surfaces.
At present, using a unique technique to organize molecules, scientists at Northwestern University have developed a material that works even better than the glue they were attempting to replicate. Their results, reported in the March 3rd issue of the Journal of the American Chemical Society, expand on how these protein-like polymers can be employed as a platform to develop 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. And keep other molecules nearby in one place, which would be useful in wound healing or repair.
Nathan Gianneschi, Study Lead and Jacob and Rosaline Cohn Professor of Chemistry, Weinberg College of Arts and Sciences, Northwestern University
Proteins like those discharged by mussel feet are present in nature. Evolution has made a custom of fashioning these long, linear chains of amino acids that repeat again and again (known as tandem repeat proteins, or TRPs).
Appearing from time to time strong, stretchy and sticky, the protein structures can be found in spider silk, insect wings and legs and mussel feet. Researchers are aware of the precise main sequences of amino acids that constitute many such proteins, yet have difficulty imitating the complicated natural process while still preserving the exceptional qualities.
The study’s first author Or Berger, a postdoctoral researcher in Gianneschi’s lab who explores peptides — these very strings of amino acids — formulated an idea for how to organize amino acid building blocks in a different way to reproduce the properties rather than directly copy the protein structure of the mussel.
By extracting the building block of one of the proteins (the repeat decapeptide, a 10-amino acid sequence that constitutes the mussel foot protein), and inserting it into synthetic polymer, Berger thought the properties may be improved.
As associate director of the International Institute for Nanotechnology, Gianneschi has designed most of his lab around the idea of imitating proteins in function by using polymer chemistry. Within precision therapeutics, drug therapies such as antibodies and other small molecules fight some diseases, where a nanocarrier is employed to deliver a drug to a target more efficiently.
But Gianneschi says reproducing proteins could approach biological difficulties differently, by altering interactions inside and between cells that influence the development of disease, or between tissues, cells and materials.
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, Study Lead and Jacob and Rosaline Cohn Professor of Chemistry, Weinberg College of Arts and Sciences, Northwestern University
The outcome was something that resembles a brush of peptides instead of looping together amino acids in a straight line as a chain. While the new process may seem like incorporating an extra step, forming protein-like polymers (PLPs) skips numerous steps, requiring scientists to form peptides in an easily available synthesizer and plug them into the snugly packed backbone instead of going through tiresome steps of protein expression.
To test the efficacy of the new material, the scientists applied either the polymer material or the native mussel protein to glass plates. The team positioned cells on the plates and then, after washing them, evaluated how many cells were still present, either attached or not, to gauge how well the materials worked. They learned the PLP formed a cellular superglue, leaving most of the cells attached compared to the native blend and untreated plate.
We actually didn’t mean to improve on the mussel’s properties. 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.
Or Berger, Study First Author and Postdoctoral Researcher in Gianneschi’s Lab, Northwestern University
The researchers believe that the model can be extensively used across other proteins that repeat their sequence to gain function in a new way to reproduce proteins. They theorize such a platform could work better than their native equivalents because they are denser and expandable.
Gianneschi said this is the first of many research articles to explore polymer-based protein mimics, and he is already planning applications for future materials.
Resilin, for example, a flexible protein found in the legs and wings of insects, could be utilized to create versatile drones and other robotics.
When you talk about polymers some people immediately think of plastic bags and bottles. Instead, these are very functional, advanced precision materials, made accessible.
Nathan Gianneschi, Study Lead and Jacob and Rosaline Cohn Professor of Chemistry, Weinberg College of Arts and Sciences, Northwestern University
Gianneschi and Berger are inventors on pending intellectual property in this domain. Gianneschi also is a professor of biomedical engineering and materials science and engineering in the McCormick School of Engineering and a member of the Chemistry of Life Processes Institute, the Simpson Querrey Institute, and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Gianneschi is the co-founder of a company, Grove Biopharma, that aims to create versions of these materials as translational therapeutics.
The study was directed by an all-Northwestern team with support from the labs of chemical and biological engineering professors Muzhou Wang and Danielle Tullman-Ercek. The study received support from the National Science Foundation’s Division of Materials Research (Award number 2004899).
Journal Reference:
Berger, O., et al. (2022) A Mussel Adhesive-Inspired Protemimetic Polymer. American Chemical Society. doi.org/10.1021/jacs.1c10936.