When it comes to studying lungs, people take up all of the air, but it turns out that scientists can learn a lot from lizards.

A new Princeton University study demonstrates how the brown anole lizard tackles one of nature’s most complicated issues – breathing — in the most simple way possible.

Human lungs evolve over months and years into baroque tree-like structures, whereas the anole lung develops in a matter of days into primitive lobes covered with bulbous protuberances.

While significantly less developed, these gourd-like structures allow the lizard to exchange oxygen for waste gases in the same way as human lungs do. Anole lungs also provide new inspiration for engineers creating breakthrough biotechnologies because they grow quickly by using simple mechanical processes.

“Our group is really interested in understanding lung development for engineering purposes,” says professor Celeste Nelson, the study’s principal investigator. “If we understand how lungs build themselves, then perhaps we can take advantage of the mechanisms mother nature uses to regenerate or engineer tissues.”

Whereas the lungs of birds and mammals develop great complexity through endless branching and complicated biochemical signaling, the brown anole lung develops its modest complexity through a mechanical process that the authors compared to the formation of a mesh stress ball — the type of toy found in desk drawers and instructional videos.

According to the researchers, the study, published in the journal Science Advances, is the first to look at the development of a reptile lung.

A few days after development, the anole lung appears as a hollow, elongated membrane surrounded by a homogeneous layer of smooth muscle. The lung cells release fluid during development, and the inner membrane gently inflates and thins like a balloon.

The strain acts on the smooth muscle, causing it to contract and split apart into fiber bundles, which eventually form a honeycomb-shaped mesh.

Fluid pressure continues to push the flexible membrane outward, causing it to bulge through gaps in the sinewy mesh and form fluid-filled bulbs that cover the lung.

Those bulges provide a large surface area for gas exchange. That’s the end of it. The entire process is completed within the first week of incubation and takes less than two days. After the lizard hatches, air enters the lung from the top, swirling around the chambers, and then exits.

This speed and simplicity provide a radical new design paradigm for engineers aiming to mimic nature’s shortcuts on behalf of human health. The finding also paves the way for scientists to investigate reptile development in more depth.

When Nelson first began researching chicken lungs in the late 2000s, conventional thought was that “chicken lungs were the same as mouse lungs were the same as human lungs,” Nelson explained. “And that’s not true.”

She directed her team to address fundamental questions about how the lungs of different vertebrate classes construct themselves in order to shake conventional preconceptions.

“The architecture of the bird lung is just so incredibly different from that of the mammalian lung,” Nelson added. For example, instead of a diaphragm, birds have air sacs embedded throughout their bodies that act as bellows.

Nelson argued that research needed to go deeper in order to adapt the exquisite intricacy of avian lungs for technologies that could enhance human health. Nature had solved the gas-exchange problem using two quite distinct mechanisms. What was the connection between them? And may there be other systems as well? This prompted her team to travel back in time in quest of a common ancestor. And there it was, doing what reptiles do best: hidden in plain sight.

When Michael Palmer entered the lab as a graduate student, he took on the task of arranging this study from the roots up. Alligators were far too obnoxious. Green anoles declined to reproduce. Palmer traveled to Florida in late 2019 to capture wild brown anoles after years of preparation. He and his colleague walked through the muck of a suburban park, flipping over boulders and leaves at the woods’ edge. They utilized dental floss traps to capture a dozen individuals and set them each in their own small vivarium. They then drove the creatures back to Princeton, where veterinarians and animal resources officials assisted the team in establishing a permanent anole facility.

There, Palmer started to look at the eggs to see how the organisms’ lungs were growing, like how big they got. Palmer used his observations to develop a computational model of the lung and comprehend its mechanics with the help of Andrej Komrlj, an assistant professor of mechanical and aerospace engineering, and graduate student Anvitha Sudhakar.

“We were curious if we could learn anything about the basics of lung development from studying such a simple lung,” added Palmer.

“The lizard lung develops using a very physical mechanism. A cascade of pressure-induced tensions and pressure-induced buckling.”

Within two days, the organ transformed from a flat balloon to fully formed lung. And the process was simple enough that Palmer could use his computational model to build a working replica in the lab. While the engineered system didn’t match the living system’s full complexity, it got close.

The membrane was cast by the researchers using a silicone material known as Ecoflex, which is routinely used in the film industry for makeup and special effects. They then wrapped the silicone in 3D printed muscle cells to replicate the same corrugations in the inflated silicone that Palmer discovered in the living organ. They encountered technical challenges that limited the veracity of their construct, but in the end, it was uncannily identical to a living organ.

Those innocuous backyard lizards had inspired a new type of artificial lung and a framework that engineers might enhance toward unforeseeable future goals.

“Different organisms have different organ structures, and that’s beautiful, and we can learn a lot from it,” Nelson added. “If we appreciate that there’s a lot of biodiversity that we can’t see, and we try to take advantage of it, then we as engineers will have more tools to tackle some of the major challenges that face society.”

Source: Science Advances

Image Credit: Getty

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