Tendons are able to withstand the broad range of stresses and strains via their finely tuned composition and structure. In addition, tendons undergo a coordinated set of dynamic responses, specifically collagen uncrimping, re-alignment, sliding and deformation, within the matrix. To date, a complete understanding of the hierarchical structure-function relationships in tendon is lacking. Therefore, the overall goal of this thesis was to measure tendon structure and function in a mouse supraspinatus model of altered structure, and to analyze links between mechanical properties, dynamic processes and composition/structure using a series of statistical analyses. In the studies presented here, we used novel and established methods to measure the multi-scale composition, structure and mechanical function of mouse supraspinatus tendons from wild type, collagen V heterozygous and collagen V null mice. Overall, we found that the experimental groups were mechanically inferior to the wild type group, with larger changes in both macroscale function and the dynamic responses (re-alignment, crimp, deformation, sliding). In addition, while fibril morphology was altered at both locations, the insertion site also exhibited alterations in cell and fiber morphology as well as extracellular matrix composition. Finally, using a novel regression approach, we found that the contribution of composition and structure as well as the contribution of dynamic processes to determining macroscale mechanical function was highly dependent on location and that the dynamic processes were significant mediators of the relationship between composition/structure and mechanical properties. Overall, we conclude that although collagen V is a quantitatively minor component in mature tendon/ligament, it is a major regulator of composition and structure during development which ultimately leads to mechanical function. Furthermore, we conclude that the dynamic responses to load are crucial factors in ultimately determining regionally-dependent mechanical function. This information will help to guide clinicians in developing preventative techniques and appropriate rehabilitation strategies, as well as help to define the appropriate and important parameters on which to base tissue engineering efforts for tendon augmentation or replacement. Finally, this work presents a strong foundation on which to develop future experimental and modeling efforts in order to fully understand the complex structure-function relationships present in tendon
