The proteins that stick to different particle surfaces change as the particles move into cells

What is it about?

A range of different polymers are used to stabilise nanoparticles, yet the effect of these different polymer coatings, which vary in terms of their surface charge, their water repellence, and the compactness or tightness of the polymer chains around the particle core, on the dynamics of protein binding during cellular uptake of the particles is poorly understood. Here, we used a range of different imaging methods to provide a detailed insight into how the surface chemistries used to disperse or stabilize industrially-relevant nanomaterials directly impact their agglomeration, protein binding, cellular internalization, and retention and evolution of the initially bound proteins as the particles move into and through cells. Using two colours of fluorescently-labelled serum proteins (green for the initial uptake and then red once the particles were internalised), we could track the exchange of proteins based on the relative green and red signals, shedding light for the first time on the evolution of the protein corona inside the cells following particle uptake and sub-cellular localisation. Such approaches can be partnered with toxicological and in vivo data to provide a robust basis for screening ‘safe-design’ NMs in the future.

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Photo by Dayne Topkin on Unsplash

Photo by Dayne Topkin on Unsplash

Why is it important?

Cells work effectively by comparmentalising proteins into specific locations, and there are growing concerns that some of the toxicity associated with nanomaterials may be a consequence of the fact that they transport proteins from one location to another as they move through the bloodstream and into tissues and cells. The use of a range of imaging approaches allowed us to gain new insights into how the polymer coatings stabilising particles plays a decisive role in determining waht proteins bind to the particles, and thus to their biological identity and recognition by cells. The very high resolution of the dSTORM imaging provided a novel insight into the structure and spatial distribution of both the initial and evolved coronas, resulting from the exposure of nanomaterials to differently-labeled populations of serum proteins. The nanoscopic resolution offered by dSTORM allowed demonstration of the fomation of a second layer of adsorbed proteins that were acquired by the particles following internalision by the cells, whereas previous understanding was that the corona was digested by the acidic environment of the lysosomes. This is important as it indicates that the polymer coating provides protection for the protein corona as well as for the underlying particle.

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