A mathematical model for the flow of a Casson fluid due to metachronal beating of cilia in a tube.
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ABSTRACT:
SUBMITTER: Siddiqui AM
PROVIDER: S-EPMC4350871 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Using a magneto-mechanical solid-fluid numerical model for permanently magnetic artificial cilia, we show that the metachronal motion of symmetrically beating cilia establishes a net pressure gradient in the direction of the metachronal wave, which creates a unidirectional flow. The flow generated is characterised as a function of the cilia spacing, the length of the metachronal wave, and a dimensionless parameter that characterises the relative importance of the viscous forces over the elastic forces in the cilia.
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Project description:Breaking of left-right symmetry is crucial in vertebrate development. The role of cilia-driven flow has been the subject of many recent publications, but the underlying mechanisms remain controversial. At approximately 8 days post-fertilization, after the establishment of the dorsal-ventral and anterior-posterior axes, a depressed structure is found on the ventral side of mouse embryos, termed the ventral node. Within the node, 'whirling' primary cilia, tilted towards the posterior, drive a flow implicated in the initial left-right signalling asymmetry. However, the underlying fluid mechanics have not been fully and correctly explained until recently and accurate characterization is required in determining how the flow triggers the downstream signalling cascades. Using the approximation of resistive force theory, we show how the flow is produced and calculate the optimal configuration to cause maximum flow, showing excellent agreement with in vitro measurements and numerical simulation, and paralleling recent analogue experiments. By calculating numerical solutions of the slender body theory equations, we present time-dependent physically based fluid dynamics simulations of particle pathlines in flows generated by large arrays of beating cilia, showing the far-field radial streamlines predicted by the theory.
| S-EPMC3226981 | biostudies-literature
Project description:We observed and measured the fluid flow that was generated by an artificial cilium. The cilium was composed of superparamagnetic microspheres, in which magnetic dipole moments were induced by an external magnetic field. The interaction between the dipole moments resulted in formation of long chains-cilia, and the same external magnetic field was also used to drive the cilia in a periodic manner. Asymmetric periodic motion of the cilium resulted in generation of fluid flow and net pumping of the surrounding fluid. The flow and pumping performance were closely monitored by introducing small fluorescent tracer particles into the system. By detecting their motion, the fluid flow around an individual cilium was mapped and the flow velocities measured. We confirm that symmetric periodic beating of one cilium results in vortical motion only, whereas asymmetry is required for additional translational motion. We determine the effect of asymmetry on the pumping performance of a cilium, verify the theoretically predicted optimal pumping conditions, and determine the fluid behaviour around a linear array of three neighbouring cilia. In this case, the contributions of neighbouring cilia enhance the maximal flow velocity compared with a single cilium and contribute to a more uniform translational flow above the surface.
| S-EPMC3364822 | biostudies-other
Project description:Many tissues are sensitive to mechanical stimuli; however, the mechanotransduction mechanism used by cells remains unknown in many cases. The primary cilium is a solitary, immotile microtubule-based extension present on nearly every mammalian cell which extends from the basal body. The cilium is a mechanosensitive organelle and has been shown to transduce fluid flow-induced shear stress in tissues, such as the kidney and bone. The majority of microtubules assemble from the mother centriole (basal body), contributing significantly to the anchoring of the primary cilium. Several studies have attempted to quantify the number of microtubules emanating from the basal body and the results vary depending on the cell type. It has also been shown that cellular response to shear stress depends on microtubular integrity. This study hypothesizes that changing the microtubule attachment of primary cilia in response to a mechanical stimulus could change primary cilia mechanics and, possibly, mechanosensitivity. Oscillatory fluid flow was applied to two different cell types and the microtubule attachment to the ciliary base was quantified. For the first time, an increase in microtubules around primary cilia both with time and shear rate in response to oscillatory fluid flow stimulation was demonstrated. Moreover, it is presented that the primary cilium is required for this loading-induced cellular response. This study has demonstrated a new role for the cilium in regulating alterations in the cytoplasmic microtubule network in response to mechanical stimulation, and therefore provides a new insight into how cilia may regulate its mechanics and thus the cells mechanosensitivity.
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Project description:Study questionHow does exposure to a testosterone rich environment affect the function and gene expression of human fallopian tube epithelium (hFTE)?Summary answerElevated testosterone level alters several gene transcripts that regulate cilia expression and negatively impacts the rate of cilia beating.What is known alreadyThe presence of estrogen in the follicular phase of the menstrual cycle increases the human fallopian tube ciliary beating frequency. The luteal phase, triggered by ovulation and increasing progesterone, is marked by a decrease in ciliary beating. Women with polycystic ovarian syndrome (PCOS) may have twice the serum level of testosterone than ovulatory women. To date, the effect of elevated androgens on the function of the human fallopian tube is not well-understood. We chose to examine the impact of elevated testosterone on hFTE.Study design, size, durationA prospective basic science study of human fallopian tube specimens from reproductive-aged women undergoing benign gynecologic surgery was performed. Fallopian tube removal at a large US academic center was collected and provided to us to continue with epithelium isolation and culturing. A total of 12 patients were analyzed in the study.Participants/materials, setting, methodsFallopian tube epithelium was isolated and exposed to two different conditions: normal with low testosterone concentration of 0.8 nM and PCOS-like, with high testosterone concentration of 2 nM. The study was conducted in both static and dynamic conditions in microfluidic devices for a total of 14 days, after which the tissue was collected for processing including RNA extraction, quantitative PCR and immunohistochemistry. After the first 7 days of each experiment, a sample of tissue from each condition was imaged to quantify cilia beating frequency.Main results and the role of chancehFTE exposed to the 2 nM testosterone displayed slower cilia beating, inhibited estrogen signaling and decreased expression of the ciliary marker FOXJ1 when compared to stimulation with 0.8 nM testosterone.Large scale dataN/A.Limitations, reasons for cautionThe in vivo response to elevated testosterone may differ from in vitro studies. RNA amount was limited from tissue cultured in the microfluidic devices as compared to static culture.Wider implications of the findingsUnderstanding elevated testosterone in tubal function may explain an additional contribution to subfertility in women with PCOS and other hyper-androgen disorders, aside from oligo-ovulation. Furthermore, this adds to the body of literature of fallopian tube function using a microfluidic device.Study funding/competing interest(s)NIH grants: UH3 ES029073 and R01 CA240301. There are no competing interests.
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Project description:Motile cilia are hair-like structures that move and propel fluid, playing important roles in the physiology of organs. Here, we present a protocol to visualize and measure ciliary beating and cerebrospinal fluid (CSF) flow in the telencephalon of an adult zebrafish brain explant. We describe the preparation of brain explants, the recording of ciliary beating and CSF flow, and data analysis using ImageJ and MATLAB. These imaging and analysis techniques can be directly translated to other ciliated systems. For complete details on the use and execution of this protocol, please refer to D'Gama et al. (2021).
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Project description:Motile cilia are miniature, propeller-like extensions, emanating from many cell types across the body. Their coordinated beating generates a directional fluid flow, which is essential for various biological processes, from respiration to reproduction. In the nervous system, ependymal cells extend their motile cilia into the brain ventricles and contribute to cerebrospinal fluid (CSF) flow. Although motile cilia are not the only contributors to CSF flow, their functioning is crucial, as patients with motile cilia defects develop clinical features, like hydrocephalus and scoliosis. CSF flow was suggested to primarily deliver nutrients and remove waste, but recent studies emphasized its role in brain development and function. Nevertheless, it remains poorly understood how ciliary beating generates and organizes CSF flow to fulfill these roles. Here, we study motile cilia and CSF flow in the brain ventricles of larval zebrafish. We identified that different populations of motile ciliated cells are spatially organized and generate a directional CSF flow powered by ciliary beating. Our investigations revealed that CSF flow is confined within individual ventricular cavities, with little exchange of fluid between ventricles, despite a pulsatile CSF displacement caused by the heartbeat. Interestingly, our results showed that the ventricular boundaries supporting this compartmentalized CSF flow are abolished during bodily movement, highlighting that multiple physiological processes regulate the hydrodynamics of CSF flow. Finally, we showed that perturbing cilia reduces hydrodynamic coupling between the brain ventricles and disrupts ventricular development. We propose that motile-cilia-generated flow is crucial in regulating the distribution of CSF within and across brain ventricles.
| S-EPMC6345627 | biostudies-literature
Project description:The mechanism that drives the regular beating of individual cilia and flagella, as well as dense ciliary fields, remains unclear. We describe a minimal model system, composed of microtubules and molecular motors, which self-assemble into active bundles exhibiting beating patterns reminiscent of those found in eukaryotic cilia and flagella. These observations suggest that hundreds of molecular motors, acting within an elastic microtubule bundle, spontaneously synchronize their activity to generate large-scale oscillations. Furthermore, we also demonstrate that densely packed, actively bending bundles spontaneously synchronize their beating patterns to produce collective behavior similar to metachronal waves observed in ciliary fields. The simple in vitro system described here could provide insights into beating of isolated eukaryotic cilia and flagella, as well as their synchronization in dense ciliary fields.
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Project description:Motile cilia are slender, hair-like cellular appendages that spontaneously oscillate under the action of internal molecular motors and are typically found in dense arrays. These active filaments coordinate their beating to generate metachronal waves that drive long-range fluid transport and locomotion. Until now, our understanding of their collective behavior largely comes from the study of minimal models that coarse grain the relevant biophysics and the hydrodynamics of slender structures. Here we build on a detailed biophysical model to elucidate the emergence of metachronal waves on millimeter scales from nanometer-scale motor activity inside individual cilia. Our study of a one-dimensional lattice of cilia in the presence of hydrodynamic and steric interactions reveals how metachronal waves are formed and maintained. We find that, in homogeneous beds of cilia, these interactions lead to multiple attracting states, all of which are characterized by an integer charge that is conserved. This even allows us to design initial conditions that lead to predictable emergent states. Finally, and very importantly, we show that, in nonuniform ciliary tissues, boundaries and inhomogeneities provide a robust route to metachronal waves.
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Project description:It is widely thought that Wnt/Lrp6 signaling proceeds through the cytoplasm and that motile cilia are signaling-inert nanomotors. Contrasting both views, we here show in the mucociliary epidermis of X. tropicalis embryos that motile cilia transduce a ciliary Wnt signal that is distinct from canonical β-catenin signaling. Instead, it engages a Wnt-Gsk3-Ppp1r11-Pp1 signaling axis. Mucociliary Wnt signaling is essential for ciliogenesis and it engages Lrp6 co-receptors that localize to cilia via a VxP ciliary targeting sequence. Live-cell imaging using a ciliary Gsk3 biosensor reveals an immediate response of motile cilia to Wnt ligand. Wnt treatment stimulates ciliary beating in X. tropicalis embryos and primary human airway mucociliary epithelia. Moreover, Wnt treatment improves ciliary function in X. tropicalis ciliopathy models of male infertility and primary ciliary dyskinesia (ccdc108, gas2l2). We conclude that X. tropicalis motile cilia are Wnt signaling organelles that transduce a distinct Wnt-Pp1 response.
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