Abstract:We describe an original method to measure mucus microrheology on human bronchial epithelium culture using optical tweezers. We probed rheology on the whole thickness of mucus above the epithelium and showed that mucus gradually varies in rheological response, from an elastic behavior close to the epithelium to a viscous one far away. Microrheology was also performed on mucus collected on the culture, on ex vivo mucus collected by bronchoscopy, and on another epithelium model. Differences are discussed and are … Show more
“…The frequency dependence of the moduli follows a weak power law with comparable exponents for and (see Supplementary Material S1 , Fig. S1), as recently observed in COPD sputum 29 as well as cultured mucus samples 30 . Figure 1 Sputum rheological response to strain.…”
Bronchial diseases are characterised by the weak efficiency of mucus transport through the lower airways, leading in some cases to the muco-obstruction of bronchi. It has been hypothesised that this loss of clearance results from alterations in the mucus rheology, which are reflected in sputum samples collected from patients, making sputum rheology a possible biophysical marker of these diseases and their evolution. However, previous rheological studies have focused on quasi-static viscoelastic (linear storage and loss moduli) properties only, which are not representative of the mucus mobilisation within the respiratory tract. In this paper, we extend this approach further, by analysing both quasi-static and some dynamic (flow point) properties, to assess their usability and relative performance in characterising several chronic bronchial diseases (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) and distinguishing them from healthy subjects. We demonstrate that pathologies influence substantially the linear and flow properties. Linear moduli are weakly condition-specific and even though the corresponding ranges overlap, distinct levels can be identified. This directly relates to the specific mucus structure in each case. In contrast, the flow point is found to strongly increase in muco-obstructive diseases, which may reflect the complete failure of mucociliary clearance causing episodic obstructions. These results suggest that the analysis of quasi-static and dynamic regimes in sputum rheology is in fact useful as these regimes provide complementary markers of chronic bronchial diseases.
“…The frequency dependence of the moduli follows a weak power law with comparable exponents for and (see Supplementary Material S1 , Fig. S1), as recently observed in COPD sputum 29 as well as cultured mucus samples 30 . Figure 1 Sputum rheological response to strain.…”
Bronchial diseases are characterised by the weak efficiency of mucus transport through the lower airways, leading in some cases to the muco-obstruction of bronchi. It has been hypothesised that this loss of clearance results from alterations in the mucus rheology, which are reflected in sputum samples collected from patients, making sputum rheology a possible biophysical marker of these diseases and their evolution. However, previous rheological studies have focused on quasi-static viscoelastic (linear storage and loss moduli) properties only, which are not representative of the mucus mobilisation within the respiratory tract. In this paper, we extend this approach further, by analysing both quasi-static and some dynamic (flow point) properties, to assess their usability and relative performance in characterising several chronic bronchial diseases (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) and distinguishing them from healthy subjects. We demonstrate that pathologies influence substantially the linear and flow properties. Linear moduli are weakly condition-specific and even though the corresponding ranges overlap, distinct levels can be identified. This directly relates to the specific mucus structure in each case. In contrast, the flow point is found to strongly increase in muco-obstructive diseases, which may reflect the complete failure of mucociliary clearance causing episodic obstructions. These results suggest that the analysis of quasi-static and dynamic regimes in sputum rheology is in fact useful as these regimes provide complementary markers of chronic bronchial diseases.
The respiratory tract is protected by mucus, a complex fluid transported along the epithelial surface by the coordinated beating of millions of microscopic cilia, hence the name of mucociliary clearance. Its impairment is associated with all severe chronic respiratory diseases. Yet, the relationship between ciliary density and the spatial scale of mucus transport, as well as the mechanisms that drive ciliary-beat orientations are much debated. Here, we show on polarized human bronchial epithelia that mucus swirls and circular orientational order of the underlying ciliary beats emerge and grow during ciliogenesis, until a macroscopic mucus transport is achieved for physiological ciliary densities. By establishing that the macroscopic ciliary-beat order is lost and recovered by removing and adding mucus respectively, we demonstrate that cilia/mucus hydrodynamic interactions govern the collective dynamics of ciliary-beat directions. We propose a two-dimensional model that predicts a phase diagram of mucus transport in accordance with the experiments. It paves the way to a predictive in-silico modeling of bronchial mucus transport in health and disease.
“…Second, it is likely that the cilia are more aligned in the tracheal mucosa than in epithelium samples derived from the nasal sinuses. Finally, the observations presented in [56] were made at 37 • C. An increase in temperature has recently been shown to decrease the mucus viscosity as well as elasticity on human bronchial epithelium cultures [58,59].…”
Background: Collectively coordinated ciliary activity constantly propels the airway surface liquid, which lines the luminal surface of the vertebrate respiratory system, in cranial direction – constituting mucociliary clearance, the primary defence mechanism of our airways. Our contemporary understanding on how the quantitative characteristics of the metachronal wave field determines the resulting mucociliary transport is still limited, which is partly due to the sparse availability of quantitative observational data. Methods: We employed high-speed video reflection contrast microscopy to simultaneously image and quantitatively characterize the metachronal wave field as well as the mucociliary transport in excised bovine, porcine, ovine, lapine, turkey and ostrich samples of the luminal tracheal wall. Advanced image processing techniques were used to determine the ciliary beating frequency (CBF), the velocity and the wavelength of the metachronal wave as well as the mucociliary transport velocity. Results: The mucociliary transport direction was found to strongly correlate with the mean wave propagation direction in all six species. The CBF yielded similar values (10−15 Hz) for all six species. Birds were found to exhibit considerably higher transport speeds (130−260 μm/s) than mammals (20−80 μm/s). While the average transport direction significantly deviates from the tracheal long axis (TLA) in mammals, no significant deviation from the TLA was found in birds. In comparison to mammals, longer metachronal wavelengths were found in birds. Finally, the metachronal waves were found to propagate at about 4−8 times the speed of mucociliary transport in mammals, whereas the metachronal waves propagate at about the speed of mucociliary transport in birds. Conclusions: The tracheal mucociliary clearance mechanism is based on a symplectic metachronsim in all examined species. The mucociliary transport in birds is fast and roughly follows the TLA, whereas the transport is slower and proceeds along a left-handed spiral in mammals. The longer wavelengths and the lower ratio between the metachronal wave speed and the mucociliary transport speed provide further evidence that the mucociliary clearance mechanism operates differently in birds than in mammals.
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