ScienceDaily (May 31, 2012) UCLA biochemists have designed specialized proteins that assemble themselves to form tiny molecular cages hundreds of times smaller than a single cell. The creation of these miniature structures may be the first step toward developing new methods of drug delivery or even designing artificial vaccines.

"This is the first decisive demonstration of an approach that can be used to combine protein molecules together to create a whole array of nanoscale materials," said Todd Yeates, a UCLA professor of chemistry and biochemistry and a member of the UCLA-DOE Institute of Genomics and Proteomics and the California NanoSystems Institute at UCLA.

Published June 1 in the journal Science, the research could be utilized to create cages from any number of different proteins, with potential applications across the fields of medicine and molecular biology.

UCLA graduate student Yen-Ting Lai, lead author of the study, used computer models to identify two proteins that could be combined to form perfectly shaped three-dimensional puzzle pieces. Twelve of these specialized pieces fit together to create a molecular cage a mere fraction of the size of a virus.

"If you just connect two random proteins together, you expect to get an irregular network," said Yeates, senior author of the study. "In order to control the geometry, the idea was to make a rigid link holding the two proteins in place as if they were parts of a toy puzzle."

The specifically designed proteins intermesh to form a hollow lattice that could act as a vessel for drug delivery, he said.

"In principle, it would be possible to attach a recognition sequence for cancer cells on the outside of the cage, with a toxin or some other 'magic bullet' contained inside," said Yeates. "That way, the drug could be delivered directly to certain targets like tumor cells."

At this stage, the assembled protein cages are porous enough that a drug placed inside would likely leak out during the delivery process, Lai said. His next project will involve constructing a new molecular cage with an interior that will be better sealed.

Another use for the versatile protein structures might be as artificial vaccines. Some traditional vaccines use an inactive surface protein from a virus to trick the body's immune system into thinking it is under attack. This method isn't always effective, because sometimes the protein in question doesn't look enough like the virus to trigger a strong response from the body's defenders.

However, by decorating the surface of a molecular cage with segments of virus-derived proteins, the tiny structures might better mimic a virus, stimulating an immune response even stronger than a traditional vaccine and better protecting the human recipient from illness.

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Building molecular 'cages' to fight disease