Investigating the Role of Mechanical Properties in Biological Systems

There is considerable interest in measuring, with nanoscale spatial resolution, the physical and material properties of biological membranes and whole cells because of their role in the physiology of living systems. The atomic force microscope (AFM) has proven to be particularly well-suited for biological studies because samples can be maintained in near physiological conditions to preserve sample integrity (such as in a buffer solution at a physiologically relevant pH or temperature), and the imaging process is relatively nondestructive. In this work, the mechanical properties of supported lipid bilayers and neurons were examined using AFM-based techniques. Specifically, tapping mode AFM-based techniques were used to investigate the influence of lipid composition and temperature fluctuations on the physicomechanical properties of supported lipid bilayers. Topographic images were produced by tapping mode AFM, while additional compositional contrast and mechanical information was gained from phase contrast imaging, higher harmonic imaging, and scanning probe acceleration microscopy (SPAM). Importantly, all of this data was acquired simultaneously during the tapping mode AFM imaging process and the same imaging parameters were used for each experiment so that fair mechanical comparisons could be made across experiments. Lastly, force-distance curves and force volume imaging were used to better understand the effect of microtubule disruption or stabilization on the toxic ability of amyloid-beta1-42 aggregates, which are implicated in the development of Alzheimer\u27s disease. Overall, the work presented in this dissertation improved techniques for studies in mechanobiology and examined how biologically relevant factors affect the mechanical properties of lipid membranes or whole cells