Mechanotransduction referstothe process bywhich a cell is abletotranslatemechanical stimulation into biochemical signals. In bone, mechanotransduction regulates how cells detect environmental stimuli and use these to direct towards bone deposition or resorption. The mechanical properties of bone cells have an impact on the way mechanical stimulation is sensed, however, little evidence is available about how these properties influence mechanotransduction.

The aim of the presentThesis was to quantify the mechanical properties of bone cells with a combined experimental and computational approach. Atomic force microscopy was employed to quantify the stiffness of bone cells and their glycocalyx. Changes in cell stiffness during osteocytogenesis were explored. Single molecule force spectroscopy of glycocalyx components was performed to evaluate their anchoring to the cytoskeleton. A single cell finite element model was designed to discern the contributions of sub-cellular components in response to simulated cell nano-indentation.

Wide ranges of variation were found for bone cell stiffness and a method was proposed to determine suitable sample sizes to capture population heterogeneity. Bytargeting single components ofthe bone glycocalyx, itwas possibleto hypothesise different mechanotransduction mechanisms depending on the hyaluronic acid attachmenttothe cytoskeleton. The developed computational framework showed similar results to the nano-indentation experiments and highlighted the role of the actin cytoskeleton in withstanding compression and distributing strain within the cell.