Muco-obstructive diseases like chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis cause increased mucus viscosity and inflammation. Increased mucus viscosity negatively impacts quality of life as it makes mucociliary clearance harder, while in more severe cases, unchecked inflammation can cause massive cell death, tissue failure, and swelling of the airways that may result in death. Commonly observed amongst patients with muco-obstructive diseases is the presence of micro-wounds, exposing cells such as immune cells and fibroblasts normally shielded by the epithelial barriers to mucus. The responses of immune cells (e.g., neutrophils) to high viscosity have never been characterized. In this study, we investigated the effects of elevated viscosity on neutrophils using healthy versus pathological mucus mimetics. These mucus mimetics were made either by adding long-chain polymer methylcellulose into medium, achieving viscosity that was three orders of magnitude times higher than the control, or by mixing different ratios of thiolated PEG with porcine gastric mucin (PGM) at the same elasticities, with the diseased gel being twice as viscous as the healthy gel. We used differentiated HL-60 (dHL-60) to model neutrophils. We found that dHL-60 exhibits three times higher directional persistence in a more viscoelastic environment. Typically, cells would exhibit higher directional persistence when exposed to a chemical gradient due to chemotaxis and travel along that gradient. However, what we observed was that cells would demonstrate higher directional persistence, though no preferred migration direction was observed in the population. Moreover, we also observed a 17% decrease in chromatin condensation for pathological mucus mimetics compared to the healthy controls, implying possible changes in gene expression under viscous conditions.
Guo et al. (2026) studied this question.