A Gold-Laced Protein Cage For Drug Delivery

By including gold atoms in the fabrication process, researchers in Japan and Poland have created nano-sized protein cages with ‘impossible’ geometries.

AsianScientist (May 29, 2019) – An international team of researchers has succeeded in creating a ‘protein cage’—a nanoscale structure for targeted drug delivery in the body—that is durable and can be readily assembled or disassembled. They published their results in Nature.

There are restrictions governing the shape of dice used in games—try to make a six-sided dice by replacing the square faces with triangles and you will be left with something horribly distorted. This is because there are strict geometrical rules governing the assembly of these so-called isohedra.

In nature as well, isohedral structures are found at the nanometer scale. Usually made from many protein subunits and having a hollow interior, these protein cages carry out many important tasks. The most famous examples are viruses where the protein cage acts as a carrier of viral genetic material into host cells.

Synthetic biologists are interested in making artificial protein cages, but they often run into geometry problems—some candidate proteins are automatically ruled out because they have the wrong shape and cannot assemble into cages. Another problem is complexity—most protein-protein interactions are mediated via complex networks of weak chemical bonds that are very difficult to engineer from scratch.

In the present study, researchers led by Professor Jonathan Heddle at RIKEN in Japan, with collaborators in Poland, found a way to solve both problems.

“We were able to replace the complex interactions between proteins with simple ‘staples’ based on the coordination of single gold atoms,” Heddle explained. “This simplifies the design problem and allows us to imbue the cages with new properties such as assembly and disassembly on demand.”

According to the authors, the building blocks of the protein cage are 11-membered rings, which, mathematically speaking, should be forbidden from forming symmetrical polyhedra. With the gold atoms, however, the proteins could assemble into large hollow complexes, ideal for encapsulating drugs.

The researchers noted that with their approach, proteins that were previously ignored because they had the ‘wrong’ shape can now be considered for drug delivery.

The article can be found at: Malay et al. (2019) An Ultra-stable Gold-coordinated Protein Cage Displaying Reversible Assembly.


Source: RIKEN; Photo: Pexels.
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