The in situ mechanics of cells in the annulus fibrosus of the intervertebral disc
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AbstractCells of the intervertebral disc are sparse, yet they are responsible for the secretion and organization of the extracellular matrix. Mechanical factors in vivo and in vitro influence the metabolic activity of the cells, altering the expression of key extracellular matrix molecules. Understanding the mechanobiological response is crucial to our elucidating the underlying mechanisms involved in disc degeneration and disease. However, the basic mechanisms that govern mechanical and biological interactions in situ are largely unknown. Using novel techniques of confocal microscopy, this dissertation has established that the in situ mechanical environment of cells from the annulus fibrosus cannot be directly inferred from tissue loads due to the morphological and micromechanical complexities of the cell and tissue matrix. With a systematic histological investigation, an extensive cellular matrix was described; with, variations in cell shape, arrangement of cellular processes and cytoskeletal architecture found both within and between the defined zones of the outer and inner annulus. Notably, the distinct morphology of cells from the interlamellar septae was identified and described. The in situ mechanical environment of these cells contrasted that of the cells within the lamellar layers. The interlamellar cells experienced a shear environment from the relative motion of the adjacent lamellar layers, while cells within the lamellar layer appeared protected via sliding of the collagen fibrils within the surrounding matrix. The in situ mechanical environment of cells was, therefore, found to be governed by micro and macro structural complexities of the collagen matrix. The detailed understanding of the in situ mechanical and morphological environment of the cells is essential to establishing the role of mechanical loads in low back pain and disc degeneration, and in determining the mechanotransduction mechanisms whereby these loads can alter the expression of matrix molecules. This dissertation provides the first direct knowledge of how mechanical loads applied to the whole disc are transferred to the cells in situ.
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