Investigating muscle contraction in search for an asthma remedy

Asthma affects about 7.8% of Americans. Those who suffer from the disease have chronically inflamed airways. The smooth muscle in their airways “remodels,” becoming thicker, contracting, and narrowing the airway. When confronted with asthmatic triggers like allergens, pathogens, or pollutants, the sensitive tissue contracts further.

During an asthma attack, patients can inhale therapeutics to reduce symptoms, but currently, no medications address the underlying issue: the hypercontractile smooth muscle. Beri et al. developed a 3D cantilever array to model airway smooth muscles and identified factors that increase contractility.

Their device enabling functional linear contractility of tissues (DEFLCT) hosts 96 wells for testing and is compatible with off-the-shelf assay plates for easy implementation and scalability.

“DEFLCT consists of two pillars in a well a fixed distance apart. We seeded human airway smooth muscle cells in a collagen gel and allowed them to contract around the ends of the pillars overnight before starting our treatment conditions,” said author Christopher Plunkett. “At the end of the treatment, we measure the distance between the pillars. The greater the difference between the pillars before and after treatment, the more the treatment has increased contraction in the smooth muscle cells.”

To test DEFLCT, the authors investigated the relationship between different inflammation-provoked cytokines and smooth muscle remodeling. They identified which cytokines exacerbated tissue contractility and screened inhibitors to investigate how well they prevented the hypercontractile phenotype.

“The DEFLCT system can be utilized to study any cell types where altered contractility is an essential component of the disease. Other examples include loss of skeletal or heart muscle function or modifications to fibroblasts that can result in fibrosis,” Plunkett said.

Source: “A high-throughput 3D cantilever array to model airway smooth muscle hypercontractility in asthma,” by Pranjali Beri, Christopher Plunkett, Joshua Barbara, Chien-Cheng Shih, S. Whitney Barnes, Olivia Ross, Paula Choconta, Ton Trinh, Datzael Gomez, Bella Litvin, John Walker, Minhua Qiu, Scott Hammack, and Erin Toyama, APL Bioengineering (2023). The article can be accessed at https://doi.org/10.1063/5.0132516 .