Gang Cheng at his lab

Picture this: a cargo ship sailing in the Pacific Ocean; the crude traveling in the gas pipe at a speed of 1.5m/second; the urinary catheter being filled up by yellow fluid; a nurse injecting medicine into someone’s vein…

All the above-mentioned scenarios point to the same challenge that has kept Gang Cheng and his 1,500ml brain busy for the past decade.

After studying and working abroad for nearly 20 years, Cheng left the University of Illinois Chicago to lead the biomaterials and molecular engineering laboratory with the School of Engineering at Westlake University. As the lab preparations came to a close, we sat down with Professor Cheng to hear his stories.

“To those who study biology, my research is on chemistry; to those who study chemistry, my area is Biology,” Cheng jokingly told us. Cheng was born in Raohe, Shuangyashan, a small and remote town bordering Russia.

Borders and boundaries constitute the world. In science, the boundary between macro and micro is clear. Yet that isn’t the case with what Cheng studies.

Aside from foul weather, ships that sail the sea face another challenge: biofouling. Biofouling is the accumulation of microorganisms, plants, algae, or small animals on the ship’s hull surface. They could increase the resistance of vessels in water by up to 60%, erode the structure, and impose safety concerns.

Urinary catheters face the same problem: microorganisms in the urine form a biofilm on the catheter wall and affects its performance. Currently, clinical catheters need to be replaced every 1 to 4 weeks.

The same challenge can take many forms: the calcification of artificial heart valves, the blood clotting caused by vascular stents, the scale and mold in bathrooms, even the plaque on our teeth. Biofouling is everywhere, and it has been bothering mankind for thousands of years.

Cheng devotes his time to studying the common mechanism of different biofouling phenomena. There are only four types of biomacromolecules: proteins, nucleic acids, lipids, and polysaccharides. The answer to the challenge lies in the formation of these four materials.

In 1999, Cheng graduated from the Department of Biochemical Engineering of Beijing University of Chemical Technology and joined China Huanqiu Chemical Engineering Coorporation. Three years later, he left to study microbiology engineering in the US. Later, he did his Ph.D. in chemical engineering. Such academic background put him in the unique jointing point between biology, chemistry, and engineering.

“Many biological phenomena are caused by the specific interactions of biomolecules. But this doesn’t mean that we could easily discover the approaches or mechanism to prevent the nonspecific interactions,” Cheng says.

What he means is this: even though we know how to attach one biomolecule to another, it doesn’t mean we know how to stop them from attaching.

The interaction of molecules is specific. To invent a material that is anti-biofouling, we need a mechanism that does not rely on the specific pathway or interaction, and it needs to be as widely applicable as possible.

About 25 years ago, Professor George Whitesides from Harvard proposed a theory. Taking the single protein system as an example, he proposed three rules for non-attachment: hydrophilic, hydrogen bond donor, and charge-neutral.

Charge-neutral property is probably the easiest to understand: charged particles tend to attract other molecules. The other two rules are both water-related, which suggests that forming a hydration layer on the material surface could stop biofouling from growing on it.

George Whitesides / Source: wyss.harvard.edu

Guided by this, scientists began the search for the anti-biofouling material. Polyethylene glycol was their first hope. Its water layer is formed by hydrogen bonds, and its anti-adhesion relatively weak. The structure is unstable, which means it could oxidize and break over time. Moreover, such materials are immunogenic, which compromised its usage inside organisms.

Cheng’s quest for anti-biofouling material started in his Ph.D. in the US. It was deemed impossible to develop an anti-bacteria catheter material back then.

But that didn’t stop the scientists from trying. Carboxybetaine distilled from beetroot was a promising contestant. This compound was not only charge-balanced but also had positive and negative charges evenly distributed at the molecular level. Moreover, it showed a stronger hydration effect compared to polyethylene glycol.

In laymen’s words, carboxybetaine could pull a layer of water molecules on the surface of the material. It blocks the protein from attaching and stops the biofouling formation. From there, scientists began to pay attention to zwitterionic polymers.

in 2008, Cheng successfully proved that a zwitterionic polymer material could stop pseudomonas aeruginosa biofilm from forming for ten days.

A sample of zwitterionic polymer in Cheng’s lab.

”Hydrophilic materials tend to be unstable, because they dissolve in water and move with the water as it goes,” Cheng told us.

That called for engineering, such as adding polyurethane to enhance the mechanical strength of the material. Facing polymeric materials, which are multifaceted and offer many ways to be modified, Cheng wants to find a common rule.

As he proceeded with the research, Cheng kept on breaking the records. His current record of anti-biofouling period is 6 months. It took him 12 years to go from 10 days to 6 months.

Cheng advocates for “full spectrum research” that goes from the molecular design to solving problems that occurred in application. He believes that it’s the job of a researcher to know every single link.

The exploration of the new compounds is part of building a material platform, a space where they could develop the same material for different use cases, solving problems of microorganism and algae from attaching to the ship as well as creating polymers that keep medicine intact in veins.

After all, both the sea and the veins are full of risks and uncertainties.

Injecting nanomedicines into human body is only the first step of a long and hard journey. Before reaching the destination, it could be captured by our immune system, or it might get attached to various proteins in our veins - it could easily be consumed before the effect kick in.

RNA drugs are more so than usual. It’s extremely difficult to get them inside the cells. Cheng and his team designed a protective mechanism that interacted with the cell membrane to help drugs to go through. Polymers are like the spaceship that safeguards the medicine – not only does it provides safety, but it also needs to make sure that it lands well.

Cheng: the 1% bacteria growth today usually means the 99% in the future.

As the lab is ready to be put in use, Cheng and his team are preparing on their next quest. The material they develop is likely to be applied to urinary catheter, to help sending medicine into the cells, to keep the ships safe in the storm, and to contribute to cars driven by renewable energy.

At the end of a two-hour interview, Cheng mentioned that the paper written by George Whitesides was published in an average journal, yet that didn’t stop it from carrying weight for future research for decades.

To engineering research, the world is the best journal, and the best papers are those that provide solutions that solve problems. As Cheng says himself, “our biggest joy comes from creating something that doesn’t exist in the world.”