Nature, engineered  

Nature creates the blueprint – Yan Zhao reengineers it. Zhao, a professor of chemistry at Iowa State University, is using micellar imprinting to design synthetic materials that mimic the functions of natural enzymes and antibodies. His lab’s cutting-edge techniques are driving innovation in areas related to disease and plastic recycling.

Federal funding agencies are taking notice of Zhao’s innovative work. Currently, his lab is working on three major federally funded research projects, each using micellar imprinting for a different scientific challenge.

How micellar imprinting works

Zhao’s team uses micellar imprinting – first used by his lab in 2013 – to create synthetic materials with two key functions: molecular recognition and catalysis.

The method uses specifically designed surfactants (soap-like molecules) that, when placed in water, form small spherical structures called micelles. Each micelle has a water-attracting (hydrophilic) surface and a water-repelling (hydrophobic) inside.

This is the same concept that allows soap to get grease off of a dish: oil gets trapped inside the micelle and is rinsed away with water.

To engineer the synthetic materials, the team places a template molecule inside the micelle. Once the micelle forms around the molecule and the template is removed, a pocket is left behind. This pocket matches the original molecule’s shape and chemical properties.

The result: a tailored material with the two key functions of recognizing and binding target molecules (molecular recognition) and speeding up chemical reactions (catalysis).

“We try to mimic how enzymes and antibodies work using these materials,” Zhao said. “Enzymes and antibodies are wonderful molecules generated by nature, but do have limitations. We design our materials to do similar things – to bind to or to react with specific molecules we’re interested in.”

Following are details about the three federally-funded projects his lab is investigating

Converting biomass using artificial cellulases

One of the Zhao’s lab projects, funded by the National Science Foundation (NSF), focuses on biomass conversion. It aims to break down cellulose into sugars that can be used to produce fuels and chemicals.

“Cellulose is made of glucose just like starch, but it’s connected differently, and we cannot digest it,” Zhao explained. “To break a cellulose chain down into sugars, you need catalysts called cellulases to speed up the reaction.”

Natural cellulases, however, are expensive. Zhao’s lab creates synthetic catalysts that are more robust, recyclable and enzyme-like.

“If you go from 37 to 90 degrees, you will kill cellulase,” Zhao explained. “Our synthetic catalysts or artificial cellulases are so robust that if you take them in boiling water, they are completely active.”

Iowa State University has filed a patent for the carbohydrate-processing catalyst, U.S. Patent Application No. 20220016612, and Zhao hopes to attract industrial interest.

“We hope to get industrial interest in this because we suddenly have a catalyst that can break down cellulose with enzyme-like efficiency and that can be recycled,” he said.

Protein recognition and labeling

A second NSF-funded project seeks to develop materials that bind to specific protein sequences. The goal is to detect the chemical changes that occur to proteins after they are formed in the cell.

Zhao’s team is engineering materials that can recognize and bind specific proteins by targeting short amino acid sequences.

“When proteins are produced in a cell, many go through a process called post-translational modification,” Zhao said. “During this process, enzymes can pick a specific protein among thousands, and a specific site on that protein to transform it. This is nearly impossible for chemists to do.”

Zhao’s lab creates imprinted materials using a sequence-containing molecule as a template. By designing cavities that match short peptide sequences and the labeling reagent, they can deliver the chemical label exactly to where it is intended.

“Using this technology, we can selectively label a single site on a target protein,” Zhao said. “With related materials, we can fish out a target protein from a huge mixture.”

This selective process could help purify proteins, label them for biological studies, or block proteins linked to disease.

Glycan recognition: Understanding immune responses

The third project, funded by the National Institutes of Health (NIH), focuses on glycan-binding mimics of proteins and enzymes. Zhao’s lab is developing materials that can identify specific glycan patterns and replicate the functions of the enzymes that modify them.

Glycans – complex sugars on the surfaces of cells – play a vital role in immune recognition, infection, and cell signaling.

“Before a virus or bacteria infects a cell,” Zhao said, “they first come in contact with glycans on the cell surface.”

Different organisms, including humans, birds, and swine, have distinct glycan patterns. Zhao’s goal is to design catalysts that selectively recognize and edit these patterns.

“It turns out sialic acids (a component of cellular glycan) on the cell surfaces of avian, swine, and human are linked differently, so they have different shapes,” Zhao said. “These different shapes are crucial to their recognition and infection by influenza virus.”

Nature already uses enzymes to remove sugar units from glycans one unit at a time, to recycle them within the cell.

“We design our catalysts almost any way we want to remove specific patterns,” Zhao said. “This will provide powerful tools for researchers to understand how different patterns of glycans control biological processes including bacterial and viral infection.”

Industrial applications and intellectual property

Across all three projects, Zhao’s enzyme and antibody-mimicking materials are at play.

“We have the ability to tailor the materials for different applications,” Zhao said. “It’s a very versatile platform for us to develop all sorts of biomaterials. We are also working on catalysts that help recycle plastics.”

Zhao hopes to receive recognition from industrial companies and advance his research to make a real-world application and impact. “Scientists have tried to duplicate the catalytic efficiency of enzymes for decades, but the catalysts found in the literature generally fall short drastically,” Zhao said. “We have achieved enzyme efficiency in some reactions and hope to replicate the success in many other chemically and biologically important reactions.”