Seeing cells as they are: single cell ICP-MS investigations of nanoparticle cellular uptake & distribution

Engineered and incidental nanoparticles (NPs) are increasingly discovered in the environment, leading to concerns that they may be harmful to humans and biota. Understanding the potential of NPs to interact and potentially penetrate cell barriers is critical for a full evaluation of their health and safety. Many techniques currently exist that can assess cellular uptake of NPs, but these are either bulk techniques, giving average concentration of NPs in a mass of cells, or are optical methods relying on slow and cumbersome sample preparation and analysis of individual cells.

Single-cell inductively coupled mass spectrometry (SC-ICP-MS, Figure 1) on the other hand, has the potential to revolutionise quantification of cellular load of NPs, by being a high throughput technique, thus measuring a multitude of individual cells, whilst also allowing an accurate measurement of the load within individual cells, as they “fly” through the nebuliser of the single cell ICP-MS. The method is a further development of single particle ICP-MS, a method that is well established at the University of Birmingham.

The project aims to use this novel technique, SC-ICP-MS, which is currently available in only a handful of labs around the world, in order to:

1) Gain better understanding of the effects of NP size, surface charge and functionalization on cell-nanoparticle interactions, including uptake quantity, uptake rate and sub-cellular localisation. Well characterised reference NPs (Au, Ag, TiO2), which can be synthesised “in house” will be used to assess any relationship between NP properties and cellular uptake.

2) Assess the stability of NPs within the cellular environment, by assessing changes in NP size over time, and potentially fluxes of metals from the NPs into the cell the cell. Notably the technique is capable of differentiating between dissolved and particulate metal.

3) Develop the method for assessment of biological impacts of NPs, linked directly to the distribution of NPs in different cellular components.

The project will also support UoB’s activities towards developing a better understanding of the fate and behaviour of NPs within the cellular environment and how this may vary as a function of different types of cells (e.g. single cell versus multicellular organisms, and plant versus animal cells).