Study discovers molecular properties of lung surfactants that could lead to better treatments for respiratory illnesses

A team led by University of Minnesota Twin Cities engineering researchers analyzed a lung surfactant's fundamental properties and structures—a naturally occurring substance that helps human and animal lungs expand and contract—providing insight that could eventually help scientists develop better treatments for respiratory illnesses.

The paper is published in Science Advances, a peer-reviewed, multidisciplinary scientific journal published by the American Association for the Advancement of Science.

Squares A-F shows the evolution of the crystalline structures of lung surfactant monolayers as they “finger” or elongates with increasing pressure. Scientists can better understand how lung surfactant spreads throughout the lungs and helps humans breathe easier by observing this evolution. Image credit: Zasadzinski Research Lab, University of Minnesota

Both human and animal lungs naturally produce a surfactant, a substance consisting of lipids and proteins that coat the lungs and decrease the surface tension as we inhale and exhale, making it easier to breathe.

Respiratory illnesses like pneumonia or COVID-19 can impede the lung surfactant from working correctly, leading to complications in breathing. A similar issue occurs in preterm babies, who sometimes haven't developed the ability to produce the substance and suffer from Neonatal Respiratory Distress Syndrome. Right now, treatments give humans replacement surfactants taken from animal lungs, but researchers have been working to create synthetic surfactants to treat these conditions for years.

“The main purpose of lung surfactant is to minimize the energy required to breathe,” said Cain Valtierrez-Gaytan, lead author of the paper and a PhD student in the University of Minnesota Department of Chemical Engineering and Materials Science. “As scientists, we want to determine how the various components of the surfactant interact with each other at a fundamental level so we can know what to include in a potential synthetic surfactant.”

While lung surfactant comprises many different materials, the University of Minnesota team was initially intrigued by the role of cholesterol, a type of lipid that occurs naturally in animal and human cells.

Using a Langmuir trough along with a high-resolution optical microscope, the researchers took images of a few of the lipids that make up lung surfactant—dipalmitoylphosphatidylcholine, hexadecanol or palmitic acid, and dihydro cholesterol—at the monolayer level, or a film consisting of one layer of molecules at the interface between air and water. By testing how the monolayers behaved at different temperatures and pressures, they uncovered two previously unconfirmed phenomena that align with fundamental theories in materials science. 

For one, the researchers found that the surfactants organize as equilibrium structures. If the crystalline parts of the molecules change shape and grow as pressure increases, they can go back to their original condition if that pressure is removed. This is a relatively rare occurrence, as monolayers typically don't return to their original structure once it's altered. 

The microscope images also showed that the crystalline parts of the monolayer's “finger” elongate when the pressure increases. This is due to chemical instability, which causes ice to splay out in fractals when a snowflake is formed. Knowing both of these properties helps the researchers better understand how fast the surfactant spreads across the lungs and how it reduces surface tension in the lungs. 

“We can use basic materials science theories, like instabilities and equilibrium, to understand how the lung surfactant works,” said Joe Zasadzinski, senior author of the paper and a professor in the University of Minnesota Department of Chemical Engineering and Materials Science. “Then we can make predictions based on fundamental physics about how these materials will organize, which will ultimately help us formulate the next generation of clinical surfactant materials.”

Source: University of Minnesota