For the first time, scientists have directly measured how smoking changes the mechanical behavior of human lung tissue.

Published in the Journal of the Royal Society Interface, the study (click here to read the study), directed by UC Riverside mechanical engineer Mona Eskandari, examines human lung parenchyma, the soft, spongy tissue that makes up the bulk of the lung. The researchers found that smoking substantially stiffens this tissue in ways resembling fibrosis, a disease that scars and toughens the lungs.

Using human lungs from donors who were either transplant-eligible or designated for research use, the researchers removed small square samples of the parenchyma, then mechanically stretched the tissue while measuring the force it resisted.

The differences between smokers and nonsmokers were striking. Tissue from smokers became significantly stiffer as it stretched, resisting expansion more strongly than healthy tissue. This is similar to how scar-like tissue makes breathing progressively more difficult in people with fibrosis.

Though lungs expand in many directions simultaneously with each breath, previous studies stretched tissue in only one direction or relied entirely on animal models. Eskandari’s lab instead conducted tensile tests by extending tissue along multiple axes simultaneously to better mimic the mechanics of real breathing.

The study also revealed that lungs are mechanically nonuniform. Tissue sampled from upper lung regions was generally stiffer than tissue from lower regions, even within the same lobe.
Researchers believe gravity may potentially explain the difference. Because humans stand upright, the upper lungs experience different long-term forces than the lower lungs.

Those uneven mechanics could have important medical consequences. The findings may help explain why certain forms of lung damage, including ventilator-induced lung injury, do not spread evenly throughout the organ. Some regions may be more vulnerable to overstretching than others.

The researchers also measured how much energy lung tissue loses during repeated stretching cycles. Human lung tissue dissipated more energy than researchers typically observe in mice, a finding that may help explain why animal studies do not always accurately represent human lung behavior.

That distinction is increasingly important because scientists are building sophisticated computational “digital twin” lungs designed to simulate breathing, disease progression, and medical interventions. If those models are based only on animal data, Eskandari said, they may fail to capture critical aspects of human lung mechanics and make it harder to use the findings in clinical settings.

The researchers also observed preliminary trends suggesting lungs stiffen with age, though Eskandari cautioned that additional donor samples are needed before drawing definite conclusions. Human donor lungs suitable for this kind of testing are rare, limiting the size of the study.

Even so, the work provides one of the most detailed mechanical datasets yet collected for human lung parenchyma. The findings could eventually improve computational lung models, ventilation strategies, and surgical planning tools designed to predict how diseased lungs respond to physical stress.

Eskandari is the founder of the biomechanics Experimental and Computational Health (click here to read bMECH) laboratory at UCR to explore questions about the mechanics of biological tissues. Her cutting-edge research was recently featured in New York Times bestselling author Mary Roach’s new book, Replaceable You: Adventures in Human Anatomy, which explores the evolution of mechanical breathing support.

“We are trying to understand the biological materials we are working with,” said Eskandari. “If we want ventilators and predictive tools that truly reflect how people breathe, these technological advances need to be informed by human-based lung data.”

About UC Riverside

The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California’s diverse culture, UCR’s enrollment is more than 26,000 students. The campus opened a medical school in 2013 and has reached the heart of the Coachella Valley through the UCR Palm Desert Center. The campus has an annual impact of more than $2.7 billion on the U.S. economy. To learn more, visit www.ucr.edu.