Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury

Abstract The link between the structural organization of the fibrillar components of lung extracellular matrix (ECM), local tissue stiffness and global viscoelastic behaviour is not known. Here we investigated the effect of injurious mechanical ventilation on the local lung tissue stiffness using 4D...

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Main Authors: Richard T. Deyhle, Robin Krüger, Luca Fardin, Irma Mahmutovic Persson, Jose Luis Cercos-Pita, Gaetano Perchiazzi, Andreas Menzel, Martin Bech, Lars E. Olsson, Sam Bayat
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-07218-9
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author Richard T. Deyhle
Robin Krüger
Luca Fardin
Irma Mahmutovic Persson
Jose Luis Cercos-Pita
Gaetano Perchiazzi
Andreas Menzel
Martin Bech
Lars E. Olsson
Sam Bayat
author_facet Richard T. Deyhle
Robin Krüger
Luca Fardin
Irma Mahmutovic Persson
Jose Luis Cercos-Pita
Gaetano Perchiazzi
Andreas Menzel
Martin Bech
Lars E. Olsson
Sam Bayat
author_sort Richard T. Deyhle
collection DOAJ
description Abstract The link between the structural organization of the fibrillar components of lung extracellular matrix (ECM), local tissue stiffness and global viscoelastic behaviour is not known. Here we investigated the effect of injurious mechanical ventilation on the local lung tissue stiffness using 4D synchrotron phase-contrast micro-CT, in normal lung and 7 days after intratracheal bleomycin induced lung injury in anesthetized rats. Quantitative maps of local lung strain (ε) were computed within aerated lung acini, using a stepwise image registration method. Fibrillar organization of collagen and elastin at the nanoscale was measured using synchrotron small-angle x-ray scattering (SAXS). Local microscopic tissue ε was reduced in the aerated acini of normal lungs post injurious ventilation and in bleomycin-injured lungs and was associated with an increase in dynamic elastance (H). The scattering peak angle (q) which is inversely related to fibril D-spacing, was decreased by injurious ventilation indicating an elongation of the collagen fibril spacing in both normal and bleomycin-injured lung. There was a positive relationship between collagen periodicity and global tissue elastance, while an inverse relation was observed with tissue hysteresis. Our data demonstrate the effect of both bleomycin-induced lung injury and high-strain mechanical ventilation on the nanoscale fibrillar organization of collagen and for the first time, a link between collagen D-spacing and global lung tissue stiffening and viscoelastic behaviour.
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spelling doaj-art-97a5ce5bf4cf4cc796ffddb8a6f2d28c2025-08-20T04:01:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-07218-9Nanoscale structural alteration of lung collagen in response to strain and bleomycin injuryRichard T. Deyhle0Robin Krüger1Luca Fardin2Irma Mahmutovic Persson3Jose Luis Cercos-Pita4Gaetano Perchiazzi5Andreas Menzel6Martin Bech7Lars E. Olsson8Sam Bayat9Medical Radiation Physics, Department of Translational Medicine, Faculty of Medicine, Lund UniversityMedical Radiation Physics, Clinical Sciences Lund, Lund UniversityUniv. Grenoble Alpes, Inserm UA07 STROBE LaboratoryMedical Radiation Physics, Department of Translational Medicine, Faculty of Medicine, Lund UniversityHedenstierna Laboratory, Uppsala UniversityHedenstierna Laboratory, Uppsala UniversityPaul Scherrer InstituteMedical Radiation Physics, Clinical Sciences Lund, Lund UniversityMedical Radiation Physics, Department of Translational Medicine, Faculty of Medicine, Lund UniversityUniv. Grenoble Alpes, Inserm UA07 STROBE LaboratoryAbstract The link between the structural organization of the fibrillar components of lung extracellular matrix (ECM), local tissue stiffness and global viscoelastic behaviour is not known. Here we investigated the effect of injurious mechanical ventilation on the local lung tissue stiffness using 4D synchrotron phase-contrast micro-CT, in normal lung and 7 days after intratracheal bleomycin induced lung injury in anesthetized rats. Quantitative maps of local lung strain (ε) were computed within aerated lung acini, using a stepwise image registration method. Fibrillar organization of collagen and elastin at the nanoscale was measured using synchrotron small-angle x-ray scattering (SAXS). Local microscopic tissue ε was reduced in the aerated acini of normal lungs post injurious ventilation and in bleomycin-injured lungs and was associated with an increase in dynamic elastance (H). The scattering peak angle (q) which is inversely related to fibril D-spacing, was decreased by injurious ventilation indicating an elongation of the collagen fibril spacing in both normal and bleomycin-injured lung. There was a positive relationship between collagen periodicity and global tissue elastance, while an inverse relation was observed with tissue hysteresis. Our data demonstrate the effect of both bleomycin-induced lung injury and high-strain mechanical ventilation on the nanoscale fibrillar organization of collagen and for the first time, a link between collagen D-spacing and global lung tissue stiffening and viscoelastic behaviour.https://doi.org/10.1038/s41598-025-07218-9Ventilator-induced lung injuryX-ray microscopySmall-angle x-ray scatteringCollagenElastin
spellingShingle Richard T. Deyhle
Robin Krüger
Luca Fardin
Irma Mahmutovic Persson
Jose Luis Cercos-Pita
Gaetano Perchiazzi
Andreas Menzel
Martin Bech
Lars E. Olsson
Sam Bayat
Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury
Scientific Reports
Ventilator-induced lung injury
X-ray microscopy
Small-angle x-ray scattering
Collagen
Elastin
title Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury
title_full Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury
title_fullStr Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury
title_full_unstemmed Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury
title_short Nanoscale structural alteration of lung collagen in response to strain and bleomycin injury
title_sort nanoscale structural alteration of lung collagen in response to strain and bleomycin injury
topic Ventilator-induced lung injury
X-ray microscopy
Small-angle x-ray scattering
Collagen
Elastin
url https://doi.org/10.1038/s41598-025-07218-9
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