Shear-Induced Anisotropy in Lung Mucus Reveals Active Structural Reorganization

Mucus transport is essential for lung health, as ciliated cells constantly propel mucus outward to clear bacteria, viruses, and particulates. While bulk rheology is well studied, mucus anisotropy—direction-dependent mechanical behavior—remains poorly understood. Such anisotropy could strongly influence ciliary-driven clearance and microbial transport, yet its origins and physiological relevance are unknown. Here, we combine bulk rheology, particle-tracking microrheology, and theoretical modeling to probe how directional stress reorganizes the mucin network. Bulk measurements under pre-stress and cyclic loading reveal strain stiffening, quantified by a differential modulus and stiffening parameter, while microrheology shows shear-induced alignment and directional dependence. We interpret these findings using a transient network model, in which mucus polymers continuously break and reform connections during deformation. The model captures how shear induces transient anisotropy that relaxes as the network reorganizes. Together, experiments and modeling show that physiologically relevant shear, such as that from ciliary beating, can transform mucus into an anisotropic, self-organizing material rather than a passive barrier.