Studying lizard lungs to build replacement human lungs.

Princeton researchers are looking at the fast-growing lungs of ordinary, common lizards called brown anoles to find way to quickly create replacement lungs for humans in need of transplants:

Whereas human lungs develop over months and years into baroque tree-like structures, the anole lung develops in just a few days into crude lobes covered with bulbous protuberances. These gourd-like structures, while far less refined, allow the lizard to exchange oxygen for waste gases just as human lungs do. And because they grow quickly by leveraging simple mechanical processes, anole lungs provide new inspiration for engineers designing advanced biotechnologies.

“Our group is really interested in understanding lung development for engineering purposes,” said Celeste Nelson, the Wilke Family Professor in Bioengineering and the principal investigator of a study published Dec. 22 in the journal Science Advances. “If we understand how lungs build themselves, then perhaps we can take advantage of the mechanisms mother nature uses to regenerate or engineer tissues.”

The anole lung starts a few days into development as a hollow, elongated membrane surrounded by a uniform layer of smooth muscle. During development, the lung cells secrete fluid, and as they do so the inner membrane slowly inflates and thins like a balloon. The pressure pushes against the smooth muscle, causing it to tighten and spread apart into fiber bundles that ultimately form a honeycomb-shaped mesh. Fluid pressure continues pushing the stretchy membrane outward, bulging through the gaps in the sinewy mesh and forming fluid-filled bulbs that cover the lung. Those bulges create lots of surface area where the gas exchange occurs.

And that’s it.

When Michael Palmer joined the lab as a graduate student, he took up the challenge of organizing this study — quite literally — from the ground up. Alligators proved too ornery. Green anoles refused to breed. After years of preliminary work, Palmer took a trip to Florida to capture wild brown anoles in late 2019. He and his colleague traipsed through the mud of a suburban park, turning over rocks and leaves along the edge of the woods. They used traps made of dental floss to capture about a dozen individuals and place them each in their own small terrarium. They then drove the animals from north Florida back to Princeton, where the University’s veterinarians and animal resources staff helped the team establish a permanent anole facility.

That’s when Palmer started looking at the eggs to map the organisms’ lung development. Working with Andrej Košmrlj, an assistant professor of mechanical and aerospace engineering, as well as graduate student Anvitha Sudhakar, Palmer used his observations to build a computational model of the lung and understand its physics.

“We were curious if we could learn anything about the basics of lung development from studying such a simple lung,” said Palmer, who earned his Ph.D. in chemical and biological engineering earlier this year. He had seen evidence that smooth muscle played a sculpting role in other systems, but in this study, he was able to observe how that worked directly.

“The lizard lung develops using a very physical mechanism,” Palmer said. “A cascade of pressure-induced tensions and pressure-induced buckling.” In less than two days, the organ goes from flat balloon to fully formed lung. And the process is simple enough that Palmer could use his computational model to build a working replica in the lab.

You can read the anole-inspired replacement-lung research here, in Science Advances.