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Analysis of Pyomelanin-Extracellular Matrix Interactions

29 Pages Posted: 24 May 2023 Publication Status: Preprint

See all articles by Rebecca F. Shepherd

Rebecca F. Shepherd

Lancaster University

Hanaa A. Galeb

Lancaster University

Jade Bentham

Lancaster University

Reza Moshrefi

Memorial University of Newfoundland (MUN)

Katelyn Ryan

Memorial University of Newfoundland (MUN)

Nur A. B. C. A. Tantowi

Lancaster University

Sara J. Baldock

Lancaster University

Nathan R. Halcovitch

Lancaster University

T. Stockmann

Lancaster University

John G. Hardy

Department of Chemistry, Lancaster University

Jemma Kerns

Lancaster University - Faculty of Health and Medicine

Adam M. Taylor

Lancaster University

Abstract

Melanins are conjugated biopolymers with varying compositions and functions, found in various tissues throughout the body. Here we examine the conjugated polymers derived from homogentisic acid (HGA), polyHGA (a simplified model of pyomelanin), formed in an ex vivo tendon model with a view to understanding interactions between melanins and the extracellular matrix (ECM) using a selection of different analytical techniques, including spectroscopy (energy dispersive X-ray, infrared and Raman), X-ray diffraction and microscopy (electron, optical and scanning electrochemical). The combination of techniques facilitated an understanding of subtle differences in the composition and distribution of ECM components, hydroxyapatite and melanin in the tendons. PolyHGA deposition in connective tissues in patients with AKU is a significant burden and cause of multiple tendon ruptures due to the significant alterations in collagen properties. Similar pathology is seen in the wider population from calcific tendinitis as a result of hydroxyapatite crystal deposition in tendons of the shoulder and lower limbs, in particular.

Note:
Funding declaration: We thank the Ministry of Education of Saudi Arabia and King Abdulaziz University for financial support for H.A.G. (Grant: KAU1526). J.G.H. thanks the UK Engineering and Physical Sciences Research Council for financial support (via grants EP/R003823/1, EP/R511560/1 and EP/K03099X/1), and the UK Biotechnology and Biological Sciences Research Council for financial support (via grant BB/L0137971/1) and the UK Royal Society for financial support (via grant: RG160449). J.G.K and A.M.T thank the Nuffield Foundation for funding through the Nuffield Research Placement programme to support J.B. TJS would like to thank the Natural Sciences and Engineering Research Council (NSERC) for a Discovery Grant (#006074-2019) as well as Memorial University of Newfoundland for startup funding.

Conflict of Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Ethical Approval: Samples were collected in accordance with UK food and farming standards.

Keywords: Alkaptonuria, Extracellular matrix, Scanning Electrochemical Microscopy

Suggested Citation

Shepherd, Rebecca F. and Galeb, Hanaa A. and Bentham, Jade and Moshrefi, Reza and Ryan, Katelyn and Tantowi, Nur A. B. C. A. and Baldock, Sara J. and Halcovitch, Nathan R. and Stockmann, T. and Hardy, John G. and Kerns, Jemma and Taylor, Adam M., Analysis of Pyomelanin-Extracellular Matrix Interactions. Available at SSRN: https://ssrn.com/abstract=4443073 or http://dx.doi.org/10.2139/ssrn.4443073

Rebecca F. Shepherd

Lancaster University ( email )

Lancaster LA1 4YX
United Kingdom

Hanaa A. Galeb

Lancaster University ( email )

Lancaster LA1 4YX
United Kingdom

Jade Bentham

Lancaster University ( email )

Lancaster LA1 4YX
United Kingdom

Reza Moshrefi

Memorial University of Newfoundland (MUN) ( email )

Katelyn Ryan

Memorial University of Newfoundland (MUN) ( email )

Nur A. B. C. A. Tantowi

Lancaster University ( email )

Lancaster LA1 4YX
United Kingdom

Sara J. Baldock

Lancaster University ( email )

Lancaster LA1 4YX
United Kingdom

Nathan R. Halcovitch

Lancaster University ( email )

Lancaster LA1 4YX
United Kingdom

T. Stockmann

Lancaster University ( email )

John G. Hardy (Contact Author)

Department of Chemistry, Lancaster University

Jemma Kerns

Lancaster University - Faculty of Health and Medicine ( email )

Adam M. Taylor

Lancaster University ( email )

Lancaster LA1 4YX
United Kingdom

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