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Structure-function Specialisation of the Interfascicular Matrix in the Human Achilles Tendon

Dharmesh Patel, View ORCID ProfileDanae E. Zamboulis, Ewa M Spiesz, Deborah Simpson, View ORCID ProfileHelen L. Birch, View ORCID ProfilePeter D. Clegg, View ORCID ProfileChavaunne T. Thorpe, View ORCID ProfileHazel R.C. Screen
doi: https://doi.org/10.1101/2021.02.22.432199
Dharmesh Patel
1Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK
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Danae E. Zamboulis
2Department of Musculoskeletal Biology, Institute of Life Course and Medical Sciences, University of Liverpool, West Derby Street, Liverpool, L7 8TX, UK
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Ewa M Spiesz
3Department of Bionanoscience, Delft University of Technology, Building 58, Van der Maasweg 9, 2629 HZ Delft, The Netherlands
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Deborah Simpson
4Centre for Proteome Research, Biosciences Building, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK
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Helen L. Birch
5Institute of Orthopaedics and Musculoskeletal Science, UCL, Stanmore Campus, Brockley Hill, Stanmore, Middlesex, HA7 4LP, UK
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Peter D. Clegg
2Department of Musculoskeletal Biology, Institute of Life Course and Medical Sciences, University of Liverpool, West Derby Street, Liverpool, L7 8TX, UK
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Chavaunne T. Thorpe
6Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU, UK
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Hazel R.C. Screen
1Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK
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  • For correspondence: h.r.c.screen@qmul.ac.uk
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ABSTRACT

Objective Tendon consists of highly aligned collagen-rich fascicles surrounded by interfascicular matrix (IFM). Some tendons act as energy stores to improve locomotion efficiency; these tendons are prone to debilitating injuries, the incidence of which increases with ageing. In equine tendons, energy storage is achieved primarily through specialisation of the IFM. However, no studies have investigated IFM structure-function specialisation in human tendons. Here, we compare the positional anterior tibialis and energy storing Achilles tendons, testing the hypothesis that the Achilles IFM has specialised composition and mechanical properties, which are lost with ageing.

Methods We used a multidisciplinary combination of mechanical testing, immunolocalisation and proteomics to investigate structure-function specialisations in functionally distinct human tendons and how these are altered with ageing.

Results The IFM in the energy storing Achilles tendon is more elastic and fatigue resistant than the IFM in the positional anterior tibialis tendon, with a trend towards decreased fatigue resistance with age in the Achilles IFM. With ageing, alterations occur predominantly to the proteome of the Achilles IFM.

Conclusion The Achilles tendon IFM is specialised for energy storage, and changes to its proteome with ageing are likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of key energy storing specialisations and their changes with ageing offers insight towards developing effective treatments for tendinopathy.

What is already known about this subject?

  • Energy storing tendons in animals and humans are particularly prone to injury and the incidence increases with increasing age.

  • Previous work in some animal models has shown that the specialisation of tendon properties for energy storage is achieved primarily through adaptation of the interfascicular matrix, with specialisation lost in ageing. However, the structural specialisations that provide the human Achilles tendon with its energy storing ability, and how these are affected by ageing, remain to be established.

What does this study add?

  • We demonstrate that the interfascicular matrix in the human Achilles tendon is specialised for energy storing, with increased elastic recoil and fatigue resistance, and that these specialisations are partially lost with ageing, likely due to alterations to the proteome of the interfascicular matrix.

How might this impact on clinical practice or future developments?

  • Short term, the specialist IFM mechanics we have demonstrated can be detected with new developments in ultrasound functional imaging, offering improved opportunities for contextual tendinopathy diagnostics. Personalised rehabilitation programmes can now be explored and designed specifically to target IFM mechanics.

  • Longer term, the knowledge of key specialisations in injury prone energy storing tendons and how they are affected by ageing, offers crucial insight towards developing cell or tissue engineering treatments targeted at restoring tendon structure and function post-injury, specifically targeted at the IFM.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 22, 2021.
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Structure-function Specialisation of the Interfascicular Matrix in the Human Achilles Tendon
Dharmesh Patel, Danae E. Zamboulis, Ewa M Spiesz, Deborah Simpson, Helen L. Birch, Peter D. Clegg, Chavaunne T. Thorpe, Hazel R.C. Screen
bioRxiv 2021.02.22.432199; doi: https://doi.org/10.1101/2021.02.22.432199
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Structure-function Specialisation of the Interfascicular Matrix in the Human Achilles Tendon
Dharmesh Patel, Danae E. Zamboulis, Ewa M Spiesz, Deborah Simpson, Helen L. Birch, Peter D. Clegg, Chavaunne T. Thorpe, Hazel R.C. Screen
bioRxiv 2021.02.22.432199; doi: https://doi.org/10.1101/2021.02.22.432199

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