Jason Gleghorn is part of a team that recently reported new findings about the physical mechanisms underlying development of the lung's branched architecture.

Branching out

Biomedical engineering professor publishes research on development of the lung's branched architecture


3:18 p.m., Aug. 27, 2015--From the outside, lungs look like a pair of pink sponges. But inside these organs is an amazingly intricate branched structure of airways in a pattern that is nearly identical among all members of the same species. This branching pattern is critical for proper lung function and survival.

Understanding how the pattern forms could enable the design of new therapeutic approaches to reverse fetal birth defects and treat diseases that compromise lung function.

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“The embryo is the original tissue engineer,” says Jason Gleghorn, assistant professor of biomedical engineering at the University of Delaware. “If we want to functionally imitate what the embryo does, we have to understand how it does its work — how tissues and organs are formed and maintained from billions of cells in a coordinated fashion. It is not enough to just take a ‘snapshot’ of what something in the body looks like at a given point in time and replicate that state.”

Gleghorn explains that space-filling, branched networks form the basic architecture of not only the lungs but numerous other organs and glands including the kidneys, pancreas and mammary glands. 

In the developing embryo, these complex structures originate as simple epithelial tubes. To form a branched network, the initial tubular geometry is molded by a series of branching events, patterned in both space and time. 

To date, scientists investigating the developing lung have focused largely on the role of biochemical signals and genetic programs in initiating and controlling the process, which is called branching morphogenesis.

Recently, however, Gleghorn and a team of colleagues from Princeton University and the Mayo Clinic found evidence for a physical mechanism in airway morphogenesis. Their findings are reported in a paper, “Mechanically Patterning the Embryonic Airway Epithelium,” published in the July 28 issue of the Proceedings of the National Academy of Sciences.  

Using a combination of 3-D culture experiments and theoretical modeling, the researchers showed that a growth-induced buckling instability can control the formation and pattern of new epithelial branches. Tuning epithelial growth changes the wavelength of the buckling instability and thereby the branching pattern. 

“Our findings indicate that lung development is not a closed genetic system,” Gleghorn says. “We now know that physical cues also regulate the spatially patterned cell behaviors that underlie assembly of the lung, so it’s important for this phenomenon to be investigated in an integrated fashion that takes into account not only the genetic and chemical signals but also the mechanical environment of the tissue.”

Gleghorn’s current work is focused on how epithelial cells integrate physical microenvironmental cues along with chemical and genetic signals to self-assemble into functional tissues.

“Ultimately, these problems require novel quantitative techniques and collaborations among engineers, biophysicists, materials scientists, and cell and developmental biologists to parse out the complex rules that guide morphogenesis,” he says. “However, understanding these details could have significant implications for regenerative medicine and the treatment of birth defects.”

Article by Diane Kukich

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