776 research outputs found
A viscoelastic traction layer model of mucociliary flow
A new mathematical model of the transport of mucus and periciliary liquid (PCL) in the airways by cilia is presented. Mucus is represented by a linearly viscoelastic fluid, the mat of cilia is modelled as an ‘active porous medium.’ The propulsive effect of the cilia is modelled by a time-dependent force acting in a shear-thinned ‘traction layer’ between the mucus and the PCL. The effects of surface and interface tension are modelled by constraining the mucus free surface and mucus–PCL interface to be flat. It is assumed that the epithelium is impermeable to fluid. Using Fourier series, the system is converted into ODEs and solved numerically. We calculate values for mean mucus speed close to those observed by Matsui et~al. [{J. Clin. Invest.}, 102(6):1125’1131, 1998], (~40 μms−1). We obtain more detail regarding the dynamics of the flow and the nonlinear relationships between physical parameters in healthy and diseased states than in previously published models. Pressure gradients in the PCL caused by interface and surface tension are vital to ensuring efficient transport of mucus, and the role of the mucus–PCL interface appears to be to support such pressure gradients, ensuring efficient transport. Mean transport of PCL is found to be very small, consistent with previous analyses, providing insight into theories regarding the normal tonicity of PCL
Modelling mucociliary clearance
Mathematical modelling of the fluid mechanics of mucociliary clearance (MCC) is reviewed and future challenges for researchers are discussed. The morphology of the bronchial and tracheal airway surface liquid (ASL) and ciliated epithelium are briefly introduced. The cilia beat cycle, beat frequency and metachronal coordination are described, along with the rheology of the mucous layer. Theoretical modelling of MCC from the late 1960s onwards is reviewed, and distinctions between ‘phenomenological’, ‘slender body theory’ and recent ‘fluid–structure interaction’ models are explained.\ud
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The ASL consists of two layers, an overlying mucous layer and underlying watery periciliary layer (PCL) which bathes the cilia. Previous models have predicted very little transport of fluid in the PCL compared with the mucous layer. Fluorescent tracer transport experiments on human airway cultures conducted by Matsui et al. [Matsui, H., Randell, S.H., Peretti, S.W., Davis, C.W., Boucher, R.C., 1998. Coordinated clearance of periciliary liquid and mucus from airway surfaces. J. Clin. Invest. 102 (6), 1125–1131] apparently showed equal transport in both the PCL and mucous layer. Recent attempts to resolve this discrepancy by the present authors are reviewed, along with associated modelling findings. These findings have suggested new insights into the interaction of cilia with mucus due to pressure gradients associated with the flat PCL/mucus interface. This phenomenon complements previously known mechanisms for ciliary propulsion. Modelling results are related to clinical findings, in particular the increased MCC observed in patients with pseudohypoaldosteronism. Recent important advances by several groups in modelling the fluid–structure interaction by which the cilia movement and fluid transport emerge from specification of internal mechanics, viscous and elastic forces are reviewed. Finally, we discuss the limitations of existing work, and the challenges for the next generation of models, which may provide further insight into this complex and vital system
Propulsion in a viscoelastic fluid
Flagella beating in complex fluids are significantly influenced by
viscoelastic stresses. Relevant examples include the ciliary transport of
respiratory airway mucus and the motion of spermatozoa in the mucus-filled
female reproductive tract. We consider the simplest model of such propulsion
and transport in a complex fluid, a waving sheet of small amplitude free to
move in a polymeric fluid with a single relaxation time. We show that, compared
to self-propulsion in a Newtonian fluid occurring at a velocity U_N, the sheet
swims (or transports fluid) with velocity U / U_N = [1+De^2 (eta_s)/(eta)
]/[1+De^2], where eta_s is the viscosity of the Newtonian solvent, eta is the
zero-shear-rate viscosity of the polymeric fluid, and De is the Deborah number
for the wave motion, product of the wave frequency by the fluid relaxation
time. Similar expressions are derived for the rate of work of the sheet and the
mechanical efficiency of the motion. These results are shown to be independent
of the particular nonlinear constitutive equations chosen for the fluid, and
are valid for both waves of tangential and normal motion. The generalization to
more than one relaxation time is also provided. In stark contrast with the
Newtonian case, these calculations suggest that transport and locomotion in a
non-Newtonian fluid can be conveniently tuned without having to modify the
waving gait of the sheet but instead by passively modulating the material
properties of the liquid.Comment: 21 pages, 1 figur
Biological Fluid Mechanics Under the Microscope: A Tribute to John Blake
John Blake (1947--2016) was a leader in fluid mechanics, his two principal
areas of expertise being biological fluid mechanics on microscopic scales and
bubble dynamics. He produced leading research and mentored others in both
Australia, his home country, and the UK, his adopted home. This article reviews
John Blake's contributions in biological fluid mechanics, as well as giving the
author's personal viewpoint as one of the many graduate students and
researchers who benefitted from his supervision, guidance and inspiration. The
key topics from biological mechanics discussed are: `squirmer' models of
protozoa, the method of images in Stokes flow and the `blakelet' solution,
discrete cilia modelling via slender body theory, physiological flows in
respiration and reproduction, blinking stokeslets in microorganism feeding,
human sperm motility, and embryonic nodal cilia.Comment: 23 pages, 11 figures. Submitted versio
Predictive role of nasal functionality tests in the evaluation of patients before nocturnal polysomnographic recording
Obstructive sleep apnoea syndrome is a disease characterized by a collapse of the pharyngeal airway resulting in repeated episodes of airflow
cessation, oxygen desaturation, and sleep disruption. It is a common disorder affecting at least 2-4% of the adult population. The role
of nasal resistance in the pathogenesis of sleep disordered breathing and sleep apnoea has not been completely clarified. Aim of the present
study was to establish whether nasal resistance and nasal volumes, measured by means of Active Anterior Rhinomanometry and Acoustic
Rhinometry together with Muco-Ciliary Transport time play a positive predictive role in the evaluation of Obstructive sleep apnoea
syndrome patients before running a nocturnal polysomnographic recording. A retrospective study was performed analysing 223 patients
referred for suspected Obstructive sleep apnoea syndrome. All patients were submitted to complete otorhinolaryngological evaluation and
underwent nocturnal polysomnography. On the basis of polysomnographic data analysis, the apnoea-hypopnoea index and snoring index,
patients were classified into two groups: Group 1 (110/223 patients) with a diagnosis of mild-moderate Obstructive sleep apnoea syndrome
(apnoea-hypopnoea index < 30) and Group 2 (113/223 patients) affected by snoring without associated hypoxaemia/hypercapnia. A control
group of 76 subjects, not complaining of sleep disorders and free from nasal symptoms was also selected. The results showed, in all the
snoring and Obstructive sleep apnoea syndrome patients, total nasal resistance and increased Muco-Ciliary Transport time compared to
standard values. Furthermore, the apnoea-hypopnoea index was significantly higher in patients with higher nasal resistence and significantly
different between the groups. These results allow us to propose the simultaneous evaluation of nasal functions by Active Anterior
Rhinomanometry, Acoustic Rhinometry, and Muco-Ciliary Transport time in the selection of patients undergoing polysomnography
Discrete cilia modelling with singularity distributions
We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system
PDE6δ-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity
The phosphodiesterase 6 delta subunit (PDE6δ) shuttles several farnesylated cargos between membranes. The cargo sorting mechanism between cilia and other compartments is not understood. Here we show using the inositol polyphosphate 5′-phosphatase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards PDE6δ and the specificity of cargo release. High-affinity cargo is exclusively released by the ciliary transport regulator Arl3, while low-affinity cargo is released by Arl3 and its non-ciliary homologue Arl2. Structures of PDE6δ/cargo complexes reveal the molecular basis of the sorting signal which depends on the residues at the −1 and −3 positions relative to farnesylated cysteine. Structure-guided mutation allows the generation of a low-affinity INPP5E mutant which loses exclusive ciliary localization. We postulate that the affinity to PDE6δ and the release by Arl2/3 in addition to a retention signal are the determinants for cargo sorting and enrichment at its destinati
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