3D architecture of the cell with different organelles: mitochondria (green), lysosomes (purple), multivesicular bodies (red), endoplasmic reticulum (cream). Image Credit: © Burcu Kepsutlu/HZB.
Nanoparticles have the ability to make their way easily into cells. For the first time, high-resolution 3D microscopy images from BESSY II offer new insights about their distribution and function.
Nanoparticles easily penetrate cells. How they are distributed there and what they do is shown for the first time by high-resolution 3D microscopy images on BESSY II. For example, certain nanoparticles accumulate preferentially in certain organelles of the cell. This can increase the energy turnover in the cell. “The cell looks like a marathon, obviously it takes energy to absorb such nanoparticles,” says lead author James McNally.
Today, nanoparticles are not only in cosmetic products, but everywhere, in the air, in water, in the soil and in food. Because they are so tiny, they easily penetrate cells in our body. This is also of interest for medical applications: Nanoparticles coated with active ingredients could be specifically introduced into cells, for example to destroy cancer cells. However, a lot has hardly been researched: for example, how nanoparticles are distributed in the cells, what they do there and how this effect depends on their size and coating.
Overview of the entire cell
A study at BESSY II has now brought new insights, where Prof. Gerd Schneider’s team can carry out X-ray microscopy images with soft, intensive X-rays. A group around the HZB biophysicist Dr. James McNally has used X-ray microscopy to examine cells with differently coated nanoparticles. The nanoparticles were exactly the same size, but coated with different active ingredients. “X-ray microscopy offers significantly better resolutions than light microscopy and a much better overview than electron microscopy,” emphasizes Schneider.
The cell looks like it has just run a marathon, apparently, the cell requires energy to absorb such nanoparticles. – Dr James McNally, Study Lead Author and Biophysicist, Helmholtz-Zentrum Berlin
Energy storage is decreasing
“X-ray microscopy allows us to see the cell as a whole, so we were able to observe this peculiarity for the first time,” explains McNally. “We found that the uptake of nanoparticles increases the number of mitochondria and endosomes, while other organelles, namely lipid droplets and multivesicular bodies, decrease,” says Burcu Kepsutlu, who carried out the experiments for her doctorate.
“ When we go on a starvation diet or run a marathon, we see similar changes in the cell – namely an increase in mitochondria and a decrease in lipid droplets,” says McNally. “Apparently it takes energy for the cell to absorb the nanoparticles, and it feels like after a marathon.”
Accumulation in organelles
For the first time, they received complete, three-dimensional, high-resolution images of the cells with the organelles contained therein, including lipid droplets, multivesicular bodies, mitochondria and endosomes. Lipid droplets act as energy stores in the cell, while mitochondria metabolize this energy.
The analysis of the images showed: The nanoparticles accumulate preferentially in cell organelles and then change the number of certain organelles in favor of other organelles. These changes were almost independent of the respective coating of the nanoparticles. This suggests that different coatings could have similar effects. Further studies with other types of nanoparticles and in particular other cell types must show whether this effect can be generalized.
3D Image of the Cell and its Organelles
X-ray microscopy offers significantly better resolution than light microscopy, and a much better overview than electron microscopy. – Gerd Schneider, Professor, Helmholtz-Zentrum Berlin
The researchers acquired, for the first time, comprehensive, 3D, high-resolution images of the cells treated with the nanoparticles, where the organelles—including mitochondria, lipid droplets, endosomes, and multivesicular bodies—were contained within. Lipid droplets act as energy stores in the cell, while mitochondria metabolize this energy.
Accumulation of Nanoparticles
Investigation of the images revealed that the nanoparticles tend to build up preferentially within a subset of the cell organelles. Moreover, the nanoparticles alter the number of particular organelles at the cost of other organelles.
The variations in the numbers of organelles were identical irrespective of the nanoparticle coating. This shows that various different types of nanoparticle coatings may produce a similar effect. Further research with other cell types and with other nanoparticle coatings is necessary to assess how general this effect is.
Number of Lipid Droplets Decreases
“X-ray microscopy allows us to see the cell as a whole, so we were able to observe this behavior for the first time,” McNally explained.
We found that the absorption of such nanoparticles increases the number of mitochondria and endosomes, while other organelles, namely lipid droplets and multivesicular bodies, decrease. – Burcu Kepsutlu, Researcher, Helmholtz-Zentrum Berlin
Kepsutlu performed the experiments for her doctorate.
ACS Nano (2020): Cells Subject Major Changes in the Quantity of Cytoplasmic Organelles after Uptake of Gold Nanoparticles with Biologically Relevant Surface Coatings, Burcu Kepsutlu, Virginia Wycisk, Katharina Achazi, Sergey Kapishnikov, Ana Joaquina Pérez-Berná, Peter Guttmann, Antje Cossmer , Eva Pereiro, Helge Ewers, Matthias Ballauff, Gerd Schneider, James G. McNally