Brauchle, Eva, Bauer, Hannah, Fernes, Patrick, Zuk, Alexandra, Schenke-Layland, Katja and Sengle, Gerhard (2017). Raman microspectroscopy as a diagnostic tool for the non-invasive analysis of fibrillin-1 deficiency in the skin and in the in vitro skin models. Acta Biomater., 52. S. 41 - 49. OXFORD: ELSEVIER SCI LTD. ISSN 1878-7568

Full text not available from this repository.

Abstract

Fibrillin microfibrils and elastic fibers are critical determinants of elastic tissues where they define as tissue-specific architectures vital mechanical properties such as pliability and elastic recoil. Fibrillin microfibrils also facilitate elastic fiber formation and support the association of epithelial cells with the interstitial matrix. Mutations in fibrillin-1 (FBNI) are causative for the Marfan syndrome, a congenital multisystem disorder characterized by progressive deterioration of the fibrillin microfibril/ elastic fiber architecture in the cardiovascular, musculoskeletal, ocular, and dermal system. In this study, we utilized Raman microspectroscopy in combination with principal component analysis (PCA) to analyze the molecular consequences of fibrillin-1 deficiency in skin of a mouse model (GT8) of Marfan syndrome. In addition, full-thickness skin models incorporating murine wild-type and Fbn1(GT8/GT8) fibroblasts as well as human HaCaT keratinocytes were generated and analyzed. Skin models containing GT8 fibroblasts showed an altered epidermal morphology when compared to wild-type models indicating a new role for fibrillin-1 in dermal-epidermal crosstalk. Obtained Raman spectra together with PCA allowed to discriminate between healthy and deficient microfibrillar networks in murine dermis and skin models. Interestingly, results obtained from GT8 dermis and skin models showed similar alterations in molecular signatures triggered by fibrillin-1 deficiency such as amide III vibrations and decreased levels of glycan vibrations. Overall, this study indicates that Raman microspectroscopy has the potential to analyze subtle changes in fibrillin-1 microfibrils and elastic fiber networks. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. Statement of Significance Mutations in building blocks of the fibrillin microfibril/ elastic fiber network manifest in disease conditions such as aneurysms, emphysema or lax skin. Understanding how structural changes induced by fibrillin-1 mutation impact the architecture of fibrillin microfibrils, which then translates into an altered activation state of targeted growth factors, represents a huge challenge in elucidating the genotype phenotype correlations in connective tissue disorders such as Marfan syndrome. This study shows that Raman microspectroscopy is able to reveal structural changes in fibrillin-1 microfibrils and elastic fiber networks and to discriminate between normal and diseased networks in vivo and in vitro. Therefore Raman microspectroscopy may be utilized as a non-invasive and sensitive diagnostic tool to identify connective tissue disorders and monitor their disease progression. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Brauchle, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bauer, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernes, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zuk, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schenke-Layland, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sengle, GerhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-234625
DOI: 10.1016/j.actbio.2016.12.019
Journal or Publication Title: Acta Biomater.
Volume: 52
Page Range: S. 41 - 49
Date: 2017
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1878-7568
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DERMAL-EPIDERMAL JUNCTION; MARFAN-SYNDROME; EXTRACELLULAR MICROFIBRILS; BASEMENT-MEMBRANE; STEM-CELLS; SPECTROSCOPY; VIVO; IDENTIFICATION; MICROSCOPY; COLLAGENMultiple languages
Engineering, Biomedical; Materials Science, BiomaterialsMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23462

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item