Biochemists Build Largest Synthetic Molecular “Cage” Ever

Brett Smith for – Your Universe Online

Biochemists at UCLA have been working to develop a ‘cage-like’ structure made of proteins to deliver materials into cells, and on Monday, the scientists announced they have successfully developed the largest-ever self-assembling molecular cage.

According to a report from the team published in Nature Chemistry, the tiny structure is made of 24 copies of a single protein and has large openings that allow for easy entrance and exit.

UCLA professor Todd Yeates has been trying to build a self-assembling protein structure since first publishing research on them on 2001. Yeates and his peers created a self-assembling cage produced from 12 pieces that fit together like pieces of a jigsaw puzzle.

“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,” Yeates said back in 2012.

More recently, the team has been able to build a molecular cage with 24 parts, according to their Nature Chemistry report. They are presently trying to layout a molecular cage with 60 sections. Constructing ever-larger cages presented new scientific difficulties, but the even bigger sizes could carry a lot more “cargo,” the study team said.

“If you just connect two random proteins together, you expect to get an irregular network,” Yeates said in discussing his 12-piece cage. “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.”

In theory, the structures being built by the UCLA scientists should be able to deliver some kind of cargo to the interior of a cell. However, the current structures are far too porous to pull that off.

“But the design principles for making a cage that is more closed would be the same,” Yeates said.

The UCLA scientist also noted that his team could make a cage that is less secure, so when it enters a cell, it would discharge its medicine, nutrients or other cargo.

“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,” Yeates said in 2012. “That way, the drug could be delivered directly to certain targets like tumor cells.”

Yeates also mentioned that his lab’s technique could also result in the creation of artificial vaccines that would mirror what a cell sees when it’s contaminated by a virus. This new kind of vaccine would trigger a solid reaction from the immune system and possibly supply better defense against diseases than conventional vaccines.

So far, the UCLA team has only used bacterial proteins to build their structures and has expressed a desire to eventually start using human proteins.

“Our first challenge will be repeating these kinds of designs with molecules that are less likely to generate a host immune response,” Yeates said. “Generally, we want to use proteins that look like human proteins so the body does not recognize them as foreign.”


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