Mucus from human bronchial epithelial cultures: rheology and adhesion across length scales

Abstract

Mucus is a viscoelastic aqueous fluid that participates in the protective barrier of many mammals' epithelia. In the airways, together with cilia beating, mucus rheological properties are crucial for lung mucociliary function, and, when impaired, potentially participate in the onset and progression of chronic obstructive pulmonary disease (COPD). Samples of human mucus collected in vivo are inherently contaminated and are thus poorly characterized. Human bronchial epithelium (HBE) cultures, differentiated from primary cells at an air–liquid interface, are highly reliable models to assess non-contaminated mucus. In this paper, the viscoelastic properties of HBE mucus derived from healthy subjects, patients with COPD and from smokers are measured. Hallmarks of shear-thinning and elasticity are obtained at the macroscale, whereas at the microscale mucus appears as a heterogeneous medium showing an almost Newtonian behaviour in some extended regions and an elastic behaviour close to boundaries. In addition, we developed an original method to probe mucus adhesion at the microscopic scale using optical tweezers. The measured adhesion forces and the comparison with mucus-simulants rheology as well as mucus imaging collectively support a structure composed of a network of elastic adhesive filaments with a large mesh size, embedded in a very soft gel.

Editorial: theme issue on complex rheology in biological systems

“…For this theme issue, we gratefully received contributions from across the physics and life sciences with interests in biorheology ranging in length scale from the rheological properties of intracellular biomolecular networks [ 1 , 10 ] to the scale of the direct extracellular environment [ 3 , 7 , 10 , 12 , 13 , 16 ], tissues [ 3 – 5 ] and even entire organs that actively exert forces onto non-Newtonian fluids [ 6 ]. The mechanical properties at the cellular level are discussed in relationship to cancer [ 2 ], as well as in relationship to the transport of red blood cells in disordered porous environments, be it in vascular networks or in microfluidic devices.…”

“…To assess this information, the contributed review by Erlich et al [ 4 ] argues it is necessary to develop novel non-perturbative methodologies to probe the network at a small length scale. Lecinski et al address this using single-bead tracking passive rheology in live S. cerevisiae yeast cells [ 1 ], and Jory et al discuss new methodologies to probe mucus adhesion at the microscopic scale using optical tweezers [ 10 ]. Erlich and co-workers also argue the interpretation of the force–displacement measurements in such experiments relies on the development of suitable theoretical models, which face the challenge of linking the molecular topology of the network to the mechanics at the continuum level; such a modelling contribution is provided by Song and co-workers who discuss hyperelastic continuum models [ 3 ].…”

“…These activities strongly resonate with the contribution by Jory et al who have studied the adhesion of mucus at the microscopic scale and shear-thinning and elasticity at the macroscale. They discuss how rheological measurements on mucus from human bronchial epithelial cultures may be used for the diagnosis of chronic obstructive pulmonary disease [ 10 ].…”

“…haematology) is clearly a field where rheology is vital [ 5 ], but other key rheological control problems emerge in digestive [ 6 ] and reproductive biology [ 7 ]. Other biological flows contain rheologically induced structural or phase transitions, and the understanding of how biological fluids and soft solids flow and deform is a key scientific area within this collaboration of physical and life sciences (blood [ 8 ], the cytosol, silk protein solutions [ 9 ], saliva, mucus [ 10 ], synovial fluid, biofilms [ 11 – 13 ], tissue buckling [ 14 ], bacterial rheotaxis [ 15 ] and E. coli bacteria swimming in media with liquid crystalline order [ 16 ] are just some examples [ 17 ]).…”

On the role of viscoelasticity in mucociliary clearance: a hydrodynamic continuum approach

“…Although we focus mainly on the role of viscoelasticity by using the Oldroyd-B model, we have also checked the additional effect of shear-thinning, another known non-Newtonian property of mucus (Jory et al 2022). For this, we have employed the Giesekus model, which accounts accurately for both viscoelasticity and shear-thinning properties of mucus (Vasquez et al 2016;Sedaghat et al 2022).…”