Structure and function relationships of mucociliary clearance in human and rat airways

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 11, 2025

Mucociliary clearance is a vital defense mechanism of the human airways, protecting against harmful particles and infections. When this process fails, it contributes to respiratory diseases like chronic obstructive pulmonary disease (COPD) asthma. While advances in single-cell transcriptomics have revealed complexity airway composition, much what we know about how structure impacts relies on animal studies. This limits our ability create accurate human-based models diseases. Here show that airways female rats humans exhibit species-specific differences distribution ciliated secretory cells as well ciliary beat, resulting significantly higher effectiveness humans. We further reveal standard lab-grown cultures lower compared identify underlying structural differences. By combining diverse experiments physics-based modeling, establish universal benchmarks assess function, interpret preclinical models, better understand disease-specific impairments mucociliary clearance. crucial for but its structure-function relationships are not fully understood. Here, authors epithelial by mapping cilia distribution, comparing rat developing quantitative function.

Language: Английский

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Novel analytical tools reveal that local synchronization of cilia coincides with tissue-scale metachronal waves in zebrafish multiciliated epithelia

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 26, 2023

Motile cilia are hair-like cell extensions that beat periodically to generate fluid flow along various epithelial tissues within the body. In dense multiciliated carpets, were shown exhibit a remarkable coordination of their in form traveling metachronal waves, phenomenon which supposedly enhances transport. Yet, how coordinate regular epithelia move fluids remains insufficiently understood, particularly due lack rigorous quantification. We combine experiments, novel analysis tools, and theory address this knowledge gap. To investigate collective dynamics cilia, we studied zebrafish nose brain. focused mainly on nose, its conserved properties with other ciliated superior accessibility for non-invasive imaging. revealed synchronized only locally size local synchronization domains increases viscosity surrounding medium. Even though is only, observed global patterns waves across epithelium. Intriguingly, these wave direction individual fish, but different left right noses, unveiling chiral asymmetry coordination. understand implications pumping, used computational model array cilia. found prevents steric collisions, i.e., colliding each other, improves pumping hardly affects flow. conclusion, show together tissue-scale alignment coincide epithelia, enhance physiological function pumping.

Language: Английский

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Self-organized intracellular twisters

Nature Physics, Journal Year: 2024, Volume and Issue: 20(4), P. 666 - 674

Published: Jan. 25, 2024

Language: Английский

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Epithelial Na ⁺ Channels Function as Extracellular Sensors

Comprehensive physiology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 41

Published: March 29, 2024

Abstract The epithelial Na + channel (ENaC) resides on the apical surfaces of specific epithelia in vertebrates and plays a critical role extracellular fluid homeostasis. Evidence that ENaC senses external environment emerged well before molecular identity was reported three decades ago. This article discusses progress toward elucidating mechanisms through which factors regulate function, highlighting insights gained from structural studies related family members. It also reviews our understanding regulation by physiology disease. After familiarizing reader with channel's physiological roles structure, we describe central protein allostery ENaC's sensitivity to environment. We then discuss each directly channel: proteases, cations anions, shear stress, other regulators particular compartments. For regulator, initial observations led discovery, investigating mechanism, pathophysiological implications regulation. © 2024 American Physiological Society. Compr Physiol 14:5407‐5447, 2024.

Language: Английский

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Nonreciprocal interactions give rise to fast cilium synchronization in finite systems

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(40)

Published: Sept. 27, 2023

Motile cilia beat in an asymmetric fashion order to propel the surrounding fluid. When many are located on a surface, their beating can synchronize such that phases form metachronal waves. Here, we computationally study model where each cilium is represented as spherical particle, moving along tilted trajectory with position-dependent active driving force and internal drag coefficient. The thus takes into account all essential broken symmetries of ciliary beat. We show taking near-field hydrodynamic interactions, effective coupling between even over entire cycle become nonreciprocal: phase more strongly affected by adjacent one side than at same distance opposite direction. As result, synchronization starts from seed edge group propagates rapidly across system, leading time scales proportionally linear dimension system. carpet characterized three different velocities: velocity fluid transport, waves, propagation. Unlike systems reciprocal coupling, boundary effects not detrimental for synchronization, but rather enable formation initial seed.

Language: Английский

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Multiflagellate Swimming Controlled by Hydrodynamic Interactions

Physical Review Letters, Journal Year: 2024, Volume and Issue: 132(20)

Published: May 16, 2024

Many eukaryotic microorganisms propelled by multiple flagella can swim very rapidly with distinct gaits. Here, we model a three-dimensional mutiflagellate swimmer, resembling the microalgae. When are actuated synchronously, swimming efficiency be enhanced or reduced interflagella hydrodynamic interactions (HIs), determined intrinsic tilting angle of flagella. The asynchronous gait phase difference between neighboring reduce oscillatory motion via basal mechanical coupling. In presence spherical body, simulations taking into account flagella-body reveal advantage anterior configuration compared posterior configuration, where in latter case an optimal number arises. Apart from understanding role HIs multiflagellate microorganisms, this work could also guide laboratory fabrications novel microswimmers.

Language: Английский

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Hydrodynamic synchronization of elastic cilia: How surface effects determine the characteristics of metachronal waves

Physical review. E, Journal Year: 2024, Volume and Issue: 109(5)

Published: May 16, 2024

A model for coordinated motion of cilia is examined in this work. In model, wave dynamics are represented by motions microspheres elastically bound to circular orbits that inclined with respect a no-slip surface. Parameters explored analytical studies and simulations. The authors demonstrate traveling waves whose direction may be tuned the elasticity.

Language: Английский

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Synchronization and metachronal waves of elastic cilia caused by unsteady viscous flow

Physical Review Research, Journal Year: 2025, Volume and Issue: 7(1)

Published: Feb. 6, 2025

Hydrodynamic coordination of cilia is ubiquitous in biology. It commonly modeled using the steady Stokes equations. The flow around ciliated cells, however, exhibits finite-time vorticity diffusion, requiring a dynamical description. We present model elastic coupled by unsteady viscous bulk fluid. Therein, diffusion impacts qualitatively and quantitatively. In particular, pairs synchronize antiphase for long times. Moreover, metachronal waves occur chains larger than penetration depth, whereas global synchronization occurs flow. Published American Physical Society 2025

Language: Английский

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Layered aquatic microenvironments control fluctuations generated by active carpets

Physical Review Research, Journal Year: 2025, Volume and Issue: 7(1)

Published: Feb. 12, 2025

In Earth's aquatic environments and the human body, microbial swimmers often accumulate at interfaces within layered systems, forming colonies known as . These bioactive layers enhance mass transport diffusion in fluid media. Here we study hydrodynamic behavior induced by confined semi-infinite layers, such one found sea surface microlayer. By deriving analytical expressions performing numerical simulations, explore how geometrical viscous confinement (layer thickness viscosity ratio) influence fluctuations passive tracer dynamics. Our findings reveal anisotropic distributions of fluctuations, characterized three distinct regions: near fluid-fluid interface (Region I), vertical dominate; an intermediate region II), become isotropic; free III), horizontal prevail. The results also demonstrate emergence coherent vortical structures highly with roll-like patterns governed layer sharpness transitions. insights provided this work have implications for understanding biogenic flow processes natural engineered environments, offering potential applications areas ecology, biofilm management, microfluidic technologies. Published American Physical Society 2025

Language: Английский

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Twist–torsion coupling in beating axonemes

Nature Physics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Language: Английский

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