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Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging

Fibrotic scarring is prevalent in a range of collagenous tissue disorders. Understanding the role of matrix biophysics in contributing to fibrotic progression is important to develop therapies, as well as to elucidate biological mechanisms. Here, we demonstrate how microfocus small-angle X-ray scatt...

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Autores principales: Zhang, Yuezhou, Hollis, Dave, Ross, Rosie, Snow, Tim, Terrill, Nick J., Lu, Yongjie, Wang, Wen, Connelly, John, Tozzi, Gianluca, Gupta, Himadri S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911729/
https://www.ncbi.nlm.nih.gov/pubmed/35269067
http://dx.doi.org/10.3390/ma15051836
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author Zhang, Yuezhou
Hollis, Dave
Ross, Rosie
Snow, Tim
Terrill, Nick J.
Lu, Yongjie
Wang, Wen
Connelly, John
Tozzi, Gianluca
Gupta, Himadri S.
author_facet Zhang, Yuezhou
Hollis, Dave
Ross, Rosie
Snow, Tim
Terrill, Nick J.
Lu, Yongjie
Wang, Wen
Connelly, John
Tozzi, Gianluca
Gupta, Himadri S.
author_sort Zhang, Yuezhou
collection PubMed
description Fibrotic scarring is prevalent in a range of collagenous tissue disorders. Understanding the role of matrix biophysics in contributing to fibrotic progression is important to develop therapies, as well as to elucidate biological mechanisms. Here, we demonstrate how microfocus small-angle X-ray scattering (SAXS), with in situ mechanics and correlative imaging, can provide quantitative and position-resolved information on the fibrotic matrix nanostructure and its mechanical properties. We use as an example the case of keloid scarring in skin. SAXS mapping reveals heterogeneous gradients in collagen fibrillar concentration, fibril pre-strain (variations in D-period) and a new interfibrillar component likely linked to proteoglycans, indicating evidence of a complex 3D structure at the nanoscale. Furthermore, we demonstrate a proof-of-principle for a diffraction-contrast correlative imaging technique, incorporating, for the first time, DIC and SAXS, and providing an initial estimate for measuring spatially resolved fibrillar-level strain and reorientation in such heterogeneous tissues. By application of the method, we quantify (at the microscale) fibrillar reorientations, increases in fibrillar D-period variance, and increases in mean D-period under macroscopic tissue strains of ~20%. Our results open the opportunity of using synchrotron X-ray nanomechanical imaging as a quantitative tool to probe structure–function relations in keloid and other fibrotic disorders in situ.
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spelling pubmed-89117292022-03-11 Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging Zhang, Yuezhou Hollis, Dave Ross, Rosie Snow, Tim Terrill, Nick J. Lu, Yongjie Wang, Wen Connelly, John Tozzi, Gianluca Gupta, Himadri S. Materials (Basel) Article Fibrotic scarring is prevalent in a range of collagenous tissue disorders. Understanding the role of matrix biophysics in contributing to fibrotic progression is important to develop therapies, as well as to elucidate biological mechanisms. Here, we demonstrate how microfocus small-angle X-ray scattering (SAXS), with in situ mechanics and correlative imaging, can provide quantitative and position-resolved information on the fibrotic matrix nanostructure and its mechanical properties. We use as an example the case of keloid scarring in skin. SAXS mapping reveals heterogeneous gradients in collagen fibrillar concentration, fibril pre-strain (variations in D-period) and a new interfibrillar component likely linked to proteoglycans, indicating evidence of a complex 3D structure at the nanoscale. Furthermore, we demonstrate a proof-of-principle for a diffraction-contrast correlative imaging technique, incorporating, for the first time, DIC and SAXS, and providing an initial estimate for measuring spatially resolved fibrillar-level strain and reorientation in such heterogeneous tissues. By application of the method, we quantify (at the microscale) fibrillar reorientations, increases in fibrillar D-period variance, and increases in mean D-period under macroscopic tissue strains of ~20%. Our results open the opportunity of using synchrotron X-ray nanomechanical imaging as a quantitative tool to probe structure–function relations in keloid and other fibrotic disorders in situ. MDPI 2022-03-01 /pmc/articles/PMC8911729/ /pubmed/35269067 http://dx.doi.org/10.3390/ma15051836 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Yuezhou
Hollis, Dave
Ross, Rosie
Snow, Tim
Terrill, Nick J.
Lu, Yongjie
Wang, Wen
Connelly, John
Tozzi, Gianluca
Gupta, Himadri S.
Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging
title Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging
title_full Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging
title_fullStr Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging
title_full_unstemmed Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging
title_short Investigating the Fibrillar Ultrastructure and Mechanics in Keloid Scars Using In Situ Synchrotron X-ray Nanomechanical Imaging
title_sort investigating the fibrillar ultrastructure and mechanics in keloid scars using in situ synchrotron x-ray nanomechanical imaging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911729/
https://www.ncbi.nlm.nih.gov/pubmed/35269067
http://dx.doi.org/10.3390/ma15051836
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