Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells

Many preterm infants require mechanical ventilation as life-saving therapy. However, ventilation-induced overpressure can result in lung diseases. Considering the lung as a viscoelastic material, positive pressure inside the lung results in increased hydrostatic pressure and tissue compression. To e...

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Main Authors: Jonas Naumann, Nicklas Koppe, Ulrich H. Thome, Mandy Laube, Mareike Zink
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2022.964318/full
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author Jonas Naumann
Nicklas Koppe
Ulrich H. Thome
Mandy Laube
Mareike Zink
author_facet Jonas Naumann
Nicklas Koppe
Ulrich H. Thome
Mandy Laube
Mareike Zink
author_sort Jonas Naumann
collection DOAJ
description Many preterm infants require mechanical ventilation as life-saving therapy. However, ventilation-induced overpressure can result in lung diseases. Considering the lung as a viscoelastic material, positive pressure inside the lung results in increased hydrostatic pressure and tissue compression. To elucidate the effect of positive pressure on lung tissue mechanics and cell behavior, we mimic the effect of overpressure by employing an uniaxial load onto fetal and adult rat lungs with different deformation rates. Additionally, tissue expansion during tidal breathing due to a negative intrathoracic pressure was addressed by uniaxial tension. We found a hyperelastic deformation behavior of fetal tissues under compression and tension with a remarkable strain stiffening. In contrast, adult lungs exhibited a similar response only during compression. Young’s moduli were always larger during tension compared to compression, while only during compression a strong deformation-rate dependency was found. In fact, fetal lung tissue under compression showed clear viscoelastic features even for small strains. Thus, we propose that the fetal lung is much more vulnerable during inflation by mechanical ventilation compared to normal inspiration. Electrophysiological experiments with different hydrostatic pressure gradients acting on primary fetal distal lung epithelial cells revealed that the activity of the epithelial sodium channel (ENaC) and the sodium-potassium pump (Na,K-ATPase) dropped during pressures of 30 cmH2O. Thus, pressures used during mechanical ventilation might impair alveolar fluid clearance important for normal lung function.
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spelling doaj.art-1ecd587761374aae8d534f548f60136b2022-12-22T04:04:23ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-09-011010.3389/fbioe.2022.964318964318Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cellsJonas Naumann0Nicklas Koppe1Ulrich H. Thome2Mandy Laube3Mareike Zink4Research Group Biotechnology and Biomedicine, Peter-Debye-Institute for Soft Matter Physics, Leipzig University, Leipzig, GermanyResearch Group Biotechnology and Biomedicine, Peter-Debye-Institute for Soft Matter Physics, Leipzig University, Leipzig, GermanyCenter for Pediatric Research Leipzig, Department of Pediatrics, Division of Neonatology, Leipzig University, Leipzig, GermanyCenter for Pediatric Research Leipzig, Department of Pediatrics, Division of Neonatology, Leipzig University, Leipzig, GermanyResearch Group Biotechnology and Biomedicine, Peter-Debye-Institute for Soft Matter Physics, Leipzig University, Leipzig, GermanyMany preterm infants require mechanical ventilation as life-saving therapy. However, ventilation-induced overpressure can result in lung diseases. Considering the lung as a viscoelastic material, positive pressure inside the lung results in increased hydrostatic pressure and tissue compression. To elucidate the effect of positive pressure on lung tissue mechanics and cell behavior, we mimic the effect of overpressure by employing an uniaxial load onto fetal and adult rat lungs with different deformation rates. Additionally, tissue expansion during tidal breathing due to a negative intrathoracic pressure was addressed by uniaxial tension. We found a hyperelastic deformation behavior of fetal tissues under compression and tension with a remarkable strain stiffening. In contrast, adult lungs exhibited a similar response only during compression. Young’s moduli were always larger during tension compared to compression, while only during compression a strong deformation-rate dependency was found. In fact, fetal lung tissue under compression showed clear viscoelastic features even for small strains. Thus, we propose that the fetal lung is much more vulnerable during inflation by mechanical ventilation compared to normal inspiration. Electrophysiological experiments with different hydrostatic pressure gradients acting on primary fetal distal lung epithelial cells revealed that the activity of the epithelial sodium channel (ENaC) and the sodium-potassium pump (Na,K-ATPase) dropped during pressures of 30 cmH2O. Thus, pressures used during mechanical ventilation might impair alveolar fluid clearance important for normal lung function.https://www.frontiersin.org/articles/10.3389/fbioe.2022.964318/fullfetal lunglung mechanicstissue deformationalveolar epithelial cellsmechanosensitivityepithelial sodium channel
spellingShingle Jonas Naumann
Nicklas Koppe
Ulrich H. Thome
Mandy Laube
Mareike Zink
Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells
Frontiers in Bioengineering and Biotechnology
fetal lung
lung mechanics
tissue deformation
alveolar epithelial cells
mechanosensitivity
epithelial sodium channel
title Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells
title_full Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells
title_fullStr Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells
title_full_unstemmed Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells
title_short Mechanical properties of the premature lung: From tissue deformation under load to mechanosensitivity of alveolar cells
title_sort mechanical properties of the premature lung from tissue deformation under load to mechanosensitivity of alveolar cells
topic fetal lung
lung mechanics
tissue deformation
alveolar epithelial cells
mechanosensitivity
epithelial sodium channel
url https://www.frontiersin.org/articles/10.3389/fbioe.2022.964318/full
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