High resolution electron microscopy of biological systems

[摘要] This thesis demonstrates the relevance of advanced transmission electron microscopy (TEM) techniques such as aberration corrected scanning transmission electron microscopy (STEM) to the study of biological samples. By developing the application of these techniques to biologically relevant systems, this study shows how advanced EM can be an effective tool by providing insight into the structure of biological systems at the highest (i.e. atomic) resolutions. High angle annular dark field (HAADF) STEM has been used to gain insight into the core structure and iron loading mechanisms of the iron storage protein, ferritin. The iron content of ferritin was quantified using size-selected gold clusters as a mass balance, the first application of this technique to a biological sample. Preliminary structural studies of a novel colorectal cancer therapy have been undertaken, where polymeric alginate molecules chelate chemotoxic luminal iron in the colon. In particular the nano-structures built when alginates bind iron under physiological conditions have been established and investigated for the first time, using HAADF-STEM. Finally using TEM, it has been revealed for the first time the structures formed, and morphology changes induced, when proteins are encapsulated by membrane mimicking nano-discs.

[发布机构] University:University of Birmingham;Department:School of Chemistry

[关键词] Q Science;QH Natural history;QH301 Biology