Analysis of Pyomelanin-Extracellular Matrix Interactions
29 Pages Posted: 24 May 2023 Publication Status: Preprint
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.
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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
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