Tough stuff and built to last: a study of tendon microstructure, mechanics and development

  • Helena Raymond-Hayling

Student thesis: Phd


Fibrous tissues such as those found in tendon, ligament, skin and heart must withstand intense and repetitive mechanical forces to complete their function. The mechanics of fibrous tissues is dictated by the composition and structure of the extracellular matrix (ECM). ECM accounts for 70\% of animal body mass and is composed or regulated by the 500 proteins in the matrisome. These include fibrillar collagens, which shield cells from mechanical stresses that would otherwise destroy them. They are arranged in tissue-specific structures and vary in number, length and diameter throughout the body. These specific architectures of collagen fibrils are tuned to the mechanical requirements of individual tissues and provide resistance to various types of mechanical stresses. The structure of fibrous tissues and how exactly they are formed, maintained, age, and behave as a material are crucial questions in several key clinical areas. These include injury, cardiovascular disease, wound repair, cancer and ageing. To approach some of these issues, I have devised three main avenues of investigation to address these questions using tendon as a model tissue. In tendon, fibrils with a broad distribution of diameters are arranged in near-parallel crimped fibres to transmit muscular force. Tendon is used in this work as a model fibrous tissue. This is because tendons are 80\% collagen by volume and their aligned fibrils mean they are well-suited to imaging in 3D. The number and arrangement of fibrils are established \textit{in embryo}, where tendon cells deposit relatively short and narrow collagen fibrils. In embryonic studies in mouse and chicken species, the fibrils laid down in very early development are never taken away but are built upon during postnatal growth, where they grow in length and diameter with the growing skeleton to meet changing mechanical requirements. Furthermore, it was once thought that collagen in the matrix of tendon is permanent once the animal is fully grown, but recent work has identified a sacrificial pool of collagen in tendon which is regulated by the circadian clock in postnatal tendon. What effect this daily regulation of collagen has on the microstructure and mechanics of the tissue is not known. The first key question addressed in my thesis is to explore computational techniques to precisely quantify the microstructural arrangement of tendon fibrils. This includes their length, diameter, volume fraction, orientation and chirality. Existing algorithms which trace three-dimensional (3D) fibre architectures are limited in precision or scope. The work completed here addresses this question using 3D electron microscopy, together with computational modelling, to trace and measure the complex architecture of collagen fibrils in tendon. The second avenue of investigation examines the mechanical response of tendon tissue to tensile force. Using information directly obtained from the microstructure, a viscoelastic model of tendon is produced, and the loading response of tendon under cyclic loading is predicted. This model is different from existing tendon mechanical models as its inputs are microstructural data derived directly from electron microscopy, and not based on theoretical geometrical arrangements. Experimental work was also completed to validate this model, by mechanically testing \textit{ex vivo} tendons. An additional part of this section on mechanics examines the effects of circadian regulation on tissue mechanics. The final aspect of this thesis concerns how and when the complex microstructure of tendon emerges in early postnatal development. Embryonic tendon fibrils are of uniform diameter and arranged in bundles with near-hexagonal packing. In adulthood, fibrils grow in diameter and take up a larger volume fraction. The diameter distribution becomes multimodal with a persistent population of small fibrils (
Date of Award1 Aug 2023
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorKarl Kadler (Supervisor) & Tom Shearer (Supervisor)

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