Mucus is a biologically significant soft material with complex rheological properties that lines various mucosal surfaces in the body, including the lungs, eyes, gastrointestinal (GI) tract, and reproductive system. In the respiratory tract, it plays a dual role—trapping pathogens and foreign particles for removal via mucociliary clearance and coughing, while also fragmenting under certain conditions to generate pathogen-laden droplets that contribute to airborne disease transmission. Due to the interplay between viscoelasticity and surface tension, mucus exhibits distinct fragmentation behaviors compared to Newtonian fluids under shear and extensional forces. These physicochemical properties are also essential for mucus functions such as barrier formation, particle trapping, and lubrication. In this study, we formulated a synthetic mucus mimetic and systematically tuned its rheological and surface tension properties using biocompatible surfactants to better replicate native mucus behavior. Rheological and interfacial tension measurements confirmed that our formulation closely matches the physical characteristics of biological mucus. Importantly, we demonstrate that reductions in surface tension and elasticity significantly enhance droplet formation. This work provides new insight into the mechanisms governing mucus fragmentation and droplet generation, with implications for airborne disease transmission. Moreover, it presents a physiologically relevant mucus mimetic model that can be used to study mucus–pathogen interactions, develop organ-on-a-chip systems, and design more effective pulmonary drug delivery strategies.
