Imaging viscosity of intragranular mucin matrix in cystic fibrosis cells

Requena, Sebastian; Ponomarchuk, Olga; Castillo, Marlius; Rebik, Jonathan; Brochiero, Emmanuelle; Borejdo, Julian; Gryczyński, Ignacy; Dzyuba, Sergei V.; Gryczyński, Zygmunt; Grygorczyk, Ryszard; Fudala, Rafał

doi:10.1038/s41598-017-17037-2

Cited by 14 publications

(25 citation statements)

References 36 publications

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“…Aside from changes in hydration of the ASL and PCL layers, in vitro data in human bronchial epithelial cell cultures grown on an air-liquid interface and ex vivo data from TRANSATLANTIC AIRWAY CONFERENCE excised porcine and rat trachea demonstrate that changes in mucus rheology also have substantial effects on MCT rate, and can, in fact, be the dominant parameter in some anatomic locations (4,28). The intragranular mucin matrices in CF and non-CF cells are not different with regard to their maturation or swelling states, but do have distinct viscosity distributions (30). In contrast, in the absence of mature glandular secretion, as in young CF rats, PCL depletion, even when accompanied by increased solid content and acidification, is not sufficient to depress MCT rate completely.…”

Section: Functional Characterization Of Mucus Transport In Cf and Othmentioning

confidence: 96%

Functional Anatomic Imaging of the Airway Surface

2018

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The airway surface functional microanatomy, including the ciliated airway epithelium and overlying mucus layer, is a critical component of the mucociliary escalator apparatus, an innate immune defense that helps to maintain a clean environment in the respiratory tract. Many genetic and acquired respiratory diseases have underlying pathophysiological mechanisms in which constituents of the airway surface functional microanatomy are defective. For example, in cystic fibrosis, mutations in the cystic fibrosis transmembrane conductance regulator gene, which normally produces a secretory anion channel protein, result in defective anion secretion and consequent dehydrated and acidic mucosal layer overlying the airway epithelium. This thick, viscous mucus results in depressed ciliary beating and delayed mucociliary transport, trapping bacteria and other pathogens, compromising host defenses and ultimately propagating disease progression. Thus, developing tools capable of studying the airway surface microanatomy has been critical to better understanding key pathophysiological mechanisms, and may become useful tools to monitor treatment outcomes. Here, we discuss functional imaging tools to study the airway surface functional microanatomy, and how their application has contributed to an improved understanding of airway disease pathophysiology.

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Section: Functional Characterization Of Mucus Transport In Cf and Othmentioning

confidence: 96%

Functional Anatomic Imaging of the Airway Surface

2018

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“…To this end, macro and microrheological data from 21 sputum and mucus surveys were evaluated. 9,10,12,13,15,23,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] The nature, origin and references of the samples selected for this analysis are listed in Supporting Information S9. were compiled.…”

Section: -Comparison With Literature Datamentioning

confidence: 99%

“…9,25 We compiled sputum and mucus rheology data coming from 21 surveys. 9,10,12,13,15,23,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Data on cystic fibrosis sputum 7,12,13,23,[27][28][29][30]32 shows a gel-like behavior with the elastic modulus ‫ܩ‬ Ԣ ሺ ߱ ሻ larger than the loss modulus ‫ܩ‬ " ሺ ߱ ሻ over the frequency range 0.01 -100 rad s -1 . At 1 rad s -1 , it is found that the averaged values of ‫ܩ‬ Ԣ and ‫ܩ‬ Ԣ Ԣ are 4.9 ± 2.2 Pa and 3.6 ± 2.4 Pa, respectively, whereas the sputum shear viscosity is estimated to be 67 ± 34 Pa s at a shear rate of 1 s -1 .…”

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confidence: 99%

Magnetic wire active microrheology of human respiratory mucus

Radiom

Hénault

Mani

et al. 2021

Preprint

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Mucus is a viscoelastic gel secreted by the pulmonary epithelium in the tracheobronchial region of the lungs. The coordinated beating of cilia in contact with the gel layer moves mucus upwards towards pharynx, removing inhaled pathogens and particles from the airways. The efficacy of this clearance mechanism depends primarily on the rheological properties of mucus. Here we use a magnetic wire-based microrheology technique to study the viscoelastic properties of human mucus collected from human bronchus tubes. The rotation versus actuation response of magnetic micron-size wires in frequency range 0.001-10 rad s-1 reveals mucus relaxation times, ranging from one to several hundred seconds. Mucus is identified as either a viscoelastic liquid with an elastic modulus of 2.5 +/-0.5 Pa and a static viscosity of 100 +/- 40 Pa s, or a soft solid with a similar elastic modulus. Our work shows that beyond the established spatial rheological property variations due to microcavities, mucus has secondary inhomogeneities which could be important in its flow properties.

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“…All airway secretory cell types differentiate from airway epithelial cells [ 23 , 24 , 25 ]. The airway mucus consists of a sol layer and a gel layer that together form a defense barrier termed the “cilia-mucus blanket” [ 26 , 27 ]. The sol layer is mainly comprised of water and is close to the surface of epithelial cells.…”

Section: The Biological Characteristics Of Mucinsmentioning

confidence: 99%

The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease

2020

Molecules

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Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

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Imaging viscosity of intragranular mucin matrix in cystic fibrosis cells

Cited by 14 publications

References 36 publications

Functional Anatomic Imaging of the Airway Surface

Functional Anatomic Imaging of the Airway Surface

Magnetic wire active microrheology of human respiratory mucus

The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease

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