Longitudinal to Transverse Metachronal Wave Transitions in an In Vitro Model of Ciliated Bronchial Epithelium.

Myriads of cilia beat on ciliated epithelia, which are ubiquitous in life. When ciliary beats are synchronized, metachronal waves emerge, whose direction of propagation depends on the living system in an unexplained way. We show on a reconstructed human bronchial epithelium in vitro that the direction of propagation is determined by the ability of mucus to be transported at the epithelial surface. Numerical simulations show that longitudinal waves maximize the transport of mucus while transverse waves, observed when the mucus is rigid and still, minimize the energy dissipated by the cilia.

Hydrodynamic model of directional ciliary-beat organization in human airways.

In the lung, the airway surface is protected by mucus, whose transport and evacuation is ensured through active ciliary beating. The mechanisms governing the long-range directional organization of ciliary beats, required for effective mucus transport, are much debated. Here, we experimentally show on human bronchial epithelium reconstituted in-vitro that the dynamics of ciliary-beat orientation is closely connected to hydrodynamic effects. To examine the fundamental mechanisms of this self-organization process, we build a two-dimensional model in which the hydrodynamic coupling between cilia is provided by a streamwise-alignment rule governing the local orientation of the ciliary forcing. The model reproduces the emergence of the mucus swirls observed in the experiments. The predicted swirl sizes, which scale with the ciliary density and mucus viscosity, are in agreement with in-vitro measurements. A transition from the swirly regime to a long-range unidirectional mucus flow allowing effective clearance occurs at high ciliary density and high mucus viscosity. In the latter case, the mucus flow tends to spontaneously align with the bronchus axis due to hydrodynamic effects.

Multigrid dual-time-stepping lattice Boltzmann method.

The lattice Boltzmann method often involves small numerical time steps due to the acoustic scaling (i.e., scaling between time step and grid size) inherent to the method. In this work, a second-order dual-time-stepping lattice Boltzmann method is proposed in order to avoid any time-step restriction. The implementation of the dual time stepping is based on an external source in the lattice Boltzmann equation, related to the time derivatives of the macroscopic flow quantities. Each time step is treated as a pseudosteady problem. The convergence rate of the steady lattice Boltzmann solver is improved by implementing a multigrid method. The developed solver is based on a two-relaxation time model coupled to an immersed-boundary method. The reliability of the method is demonstrated for steady and unsteady laminar flows past a circular cylinder, either fixed or towed in the computational domain. In the steady-flow case, the multigrid method drastically increases the convergence rate of the lattice Boltzmann method. The dual-time-stepping method is able to accurately reproduce the unsteady flows. The physical time step can be freely adjusted; its effect on the simulation cost is linear, while its impact on the accuracy follows a second-order trend. Two major advantages arise from this feature. (i) Simulation speed-up can be achieved by increasing the time step while conserving a reasonable accuracy. A speed-up of 4 is achieved for the unsteady flow past a fixed cylinder, and higher speed-ups are expected for configurations involving slower flow variations. Significant additional speed-up can also be achieved by accelerating transients. (ii) The choice of the time step allows us to alter the range of simulated timescales. In particular, increasing the time step results in the filtering of undesired pressure waves induced by sharp geometries or rapid temporal variations, without altering the main flow dynamics. These features may be critical to improve the efficiency and range of applicability of the lattice Boltzmann method.

Explicit and viscosity-independent immersed-boundary scheme for the lattice Boltzmann method.

Viscosity independence of lattice-Boltzmann methods is a crucial issue to ensure the physical relevancy of the predicted macroscopic flows over large ranges of physical parameters. The immersed-boundary (IB) method, a powerful tool that allows one to immerse arbitrary-shaped, moving, and deformable bodies in the flow, suffers from a boundary-slip error that increases as a function of the fluid viscosity, substantially limiting its range of application. In addition, low fluid viscosities may result in spurious oscillations of the macroscopic quantities in the vicinity of the immersed boundary. In this work, it is shown mathematically that the standard IB method is indeed not able to reproduce the scaling properties of the macroscopic solution, leading to a viscosity-related error on the computed IB force. The analysis allows us to propose a simple correction of the IB scheme that is local, straightforward and does not involve additional computational time. The derived method is implemented in a two-relaxation-time D2Q9 lattice-Boltzmann solver, applied to several physical configurations, namely, the Poiseuille flow, the flow around a cylinder towed in still fluid, and the flow around a cylinder oscillating in still fluid, and compared to a noncorrected immersed-boundary method. The proposed correction leads to a major improvement of the viscosity independence of the solver over a wide range of relaxation times (from 0.5001 to 50), including the correction of the boundary-slip error and the suppression of the spurious oscillations. This improvement may considerably extend the range of application of the IB lattice-Boltzmann method, in particular providing a robust tool for the numerical analysis of physical problems involving fluids of varying viscosity interacting with solid geometries.

Transport and Mixing Induced by Beating Cilia in Human Airways.

The fluid transport and mixing induced by beating cilia, present in the bronchial airways, are studied using a coupled lattice Boltzmann-Immersed Boundary solver. This solver allows the simulation of both single and multi-component fluid flows around moving solid boundaries. The cilia are modeled by a set of Lagrangian points, and Immersed Boundary forces are computed onto these points in order to ensure the no-slip velocity conditions between the cilia and the fluids. The cilia are immersed in a two-layer environment: the periciliary layer (PCL) and the mucus above it. The motion of the cilia is prescribed, as well as the phase lag between two cilia in order to obtain a typical collective motion of cilia, known as metachronal waves. The results obtained from a parametric study show that antiplectic metachronal waves are the most efficient regarding the fluid transport. A specific value of phase lag, which generates the larger mucus transport, is identified. The mixing is studied using several populations of tracers initially seeded into the pericilary liquid, in the mucus just above the PCL-mucus interface, and in the mucus far away from the interface. We observe that each zone exhibits different chaotic mixing properties. The larger mixing is obtained in the PCL layer where only a few beating cycles of the cilia are required to obtain a full mixing, while above the interface, the mixing is weaker and takes more time. Almost no mixing is observed within the mucus, and almost all the tracers do not penetrate the PCL layer. Lyapunov exponents are also computed for specific locations to assess how the mixing is performed locally. Two time scales are introduced to allow a comparison between mixing induced by fluid advection and by molecular diffusion. These results are relevant in the context of respiratory flows to investigate the transport of drugs for patients suffering from chronic respiratory diseases.

Rheological properties of synthetic mucus for airway clearance.

In this work, a complete rheological characterization of bronchial mucus simulants based on the composition proposed by Zahm et al. (Eur Respir J 1991; 4:311-315) is presented. Dynamic small amplitude oscillatory shear (SAOS) experiments, steady state (SS) flow measurements and three intervals thixotropy tests (3ITT), are carried out to investigate the global rheological complexities of simulants (viscoelasticity, viscoplasticity, shear-thinning, and thixotropy) as a function of scleroglucan concentrations (0.5-2 wt %) and under temperatures of 20 and 37°C. SAOS measurements show that the limit of the linear viscoelastic range as well as the elasticity both increase with increasing sclerogucan concentrations. Depending on the sollicitation frequency, the 0.5 wt % gel response is either liquid-like or solid-like, whereas more concentrated gels show a solid-like response over the whole frequency range. The temperature dependence of gels response is negligible in the 20-37°C range. The Herschel-Bulkley (HB) model is chosen to fit the SS flow curve of simulants. The evolution of HB parameters versus polymer concentration show that both shear-thinning and viscoplasticity increase with increasing concentrations. 3ITTs allow calculation of recovery thixotropic times after shearings at 100 or 1.6 s-1 . Empiric correlations are proposed to quantify the effect of polymer concentration on rheological parameters of mucus simulants. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 386-396, 2018.

The PELskin project: part II-investigating the physical coupling between flexible filaments in an oscillating flow.

The fluid-structure interaction mechanisms of a coating composed of flexible flaps immersed in a periodically oscillating channel flow is here studied by means of numerical simulation, employing the Euler-Bernoulli equations to account for the flexibility of the structures. A set of passively actuated flaps have previously been demonstrated to deliver favourable aerodynamic impact when attached to a bluff body undergoing periodic vortex shedding. As such, the present configuration is identified to provide a useful test-bed to better understand this mechanism, thought to be linked to experimentally observed travelling waves. Having previously validated and elucidated the flow mechanism in Paper 1 of this series, we hereby undertake a more detailed analysis of spectra obtained for different natural frequency of structures and different configurations, in order to better characterize the mechanisms involved in the organized motion of the structures. Herein, this wave-like behaviour, observed at the tips of flexible structures via interaction with the fluid flow, is characterized by examining the time history of the filaments motion and the corresponding effects on the fluid flow, in terms of dynamics and frequency of the fluid velocity. Results indicate that the wave motion behaviour is associated with the formation of vortices in the gaps between the flaps, which itself are a function of the structural resistance to the cross flow. In addition, formation of vortices upstream of the leading and downstream of the trailing flap is seen, which interact with the formation of the shear-layer on top of the row. This leads to a phase shift in the wave-type motion along the row that resembles the observation in the cylinder case.