Alexandra’s research uses high resolution electron microscopy to visualize interactions between cells and bio- or nano-materials. Her current interest is to develop novel methodologies to image nanoparticles within cellular compartments using novel TEM techniques such as 3-D electron tomography and energy-filtered TEM. The overall goal of this work is to understand the impact of synthetic nanoparticles on human health and the environment. She is also involved in applying these techniques to characterise interfaces between tissues and biomaterials (e.g. hydroxyapatite) at high resolution and to understand aging and disease of human tissues (e.g. Osteoporosis and Alzheimer’s Disease).
Zero-loss energy filtered TEM image of SWNTs inside the nucleus of a human macrophage cell (4 days exposure). Inset – individual SWNTs. c-cytoplasm.
Reconstructed phase image of apatite crystals in aged dentin (human teeth).
Contradictory data on the toxic effects of SWNTs highlights the need for alternative ways to study the uptake and cytotoxic effects of SWNTs in cells. SWNTs have been shown to be acutely toxic in a variety of cells but the direct observation of cellular uptake of SWNTs has not been demonstrated previously due to difficulties in discriminating carbon-based nanotubes from carbon-rich cell structures. We show that direct imaging to SWNTs in cells is possible using both transmission electron microscopy (TEM). The nanotubes were seen to enter the cytoplasm and localize within the cell nucleus causing cell mortality in a dose-dependent manner.
C60 particles have the potential to serve as direct drug-delivery messengers or be used for other beneficial purposes, but they can be toxic to cells. The mechanism by which the particles damage the cell depends on where they localize to within the cell. We have demonstrated that low-loss energy-filtered TEM (EFTEM) enables clear differentiation between C60 and cellular compartments. The C60 was shown to aggregate at the plasma membrane, within lysosomes and inside the cell nucleus.
The incorporation of silicon into hydroxyapatite (HA) has been shown to significantly increase the bioactivity of HA implants, but uncertainty remains about the mechanism. We compared dissolution of HA and Si-HA implanted into sheep compared using HRTEM. We showed that dissolution initiated at grain boundaries and hence the smaller grained Si-HA was more soluble. This work explains one mechanism by which silicon increases the bioactivity of HA implants.
Teaching: Biomaterials, Transmission electron microscopy graduate lecture course