Proteins are finicky molecules. When removed from their native environments, they typically fall apart. To function properly, proteins must fold into a specific structure, often with the help of other proteins.
Now a team of researchers at Northwestern University and the University of California at Berkeley have discovered a way to keep proteins active outside of a cell. The discovery could lead to a new class of materials with functions found only in living systems.
“We think we’ve cracked the code for interfacing natural and synthetic systems,” said Ting Xu, professor of materials science and engineering and chemistry at Berkeley, who led the study.
The study was published March 15 in the journal Science. Northwestern’s Monica Olvera de la Cruz led the experiment’s molecular simulations.
Monica Olvera de la Cruz is the Lawyer Taylor Professor of Materials Science and Engineering, Professor of Chemistry, Chemical and Biological Engineering, Physics and Astronomy and a resident member of the Chemistry of Life Processes Institute.
Despite years of effort to stabilize proteins outside of their native environments, scientists have made limited progress in combining proteins with synthetic components without compromising protein activity. To overcome this challenge, the researchers analyzed trends in protein sequences and surfaces to see if they could develop a synthetic polymer that provides all the things a protein would need to keep its structure and function.
“Proteins have very well-defined statistical pattern,” Xu said. “So if you can mimic that pattern, then you can marry the synthetic and natural systems, which allows us to make these materials.”
Xu’s laboratory created random heteropolymers (RHPs), which comprise four types of monomer subunits, each with chemical properties designed to interact with chemical patches on the surface of proteins of interest. When connected, the monomers mimic a natural protein to maximize the flexibility of their interactions with protein surfaces. The RHPs act as unstructured proteins, commonly seen inside cells. They increased membrane protein folding in water during protein translation and preserved water-soluble protein activity in organic solvents.
Led by Olvera de la Cruz, Northwestern’s team ran extensive molecular simulations to show that RHPs would interact favorably with protein surfaces, wrap around protein surfaces in organic solvents and adhere weakly in water, leading to correct protein folding and stability in a non-native environment.
“Our simulations show that enzymes select the sequences of hydrophobic and hydrophilic groups from the batch of random heteropolymer sequences that allow the function of enzymes in non-biological media,” Olvera de la Cruz said. “The mechanism, which is similar to the way disordered proteins concentrate enzymes in cells, will allow the formation of synthetic membranes that can make chemicals.”
The researchers then tested whether they could use RHPs to create protein-based materials for bioremediation of toxic chemicals. They mixed RHPs with a protein called organophosphorous hydrolase (OPH), which degrades the chemicals used in insecticides and chemical warfare agents. They then used the RHP/OPH combination to make fiber mats.
After submersing the mats in an insecticide, the researchers found that the mats degraded the chemical in just a few minutes. This could open the door for the creation of larger mats that could soak up and trap toxic chemicals in places such as war zones.
The study is titled “Random heteropolymers preserve protein function in foreign environments.”
The research was supported by the U.S. Department of Defense, U.S. Department of Energy and the Sherman Fairchild Foundation.
Original article published on Northwestern Now, adapted from an article by the University of California, Berkeley.