X-ray microscopy at BESSY II: Nanoparticles can change cells
3D architecture of the cell with different organelles: mitochondria (green), lysosomes (purple), multivesicular bodies (red), endoplasmic reticulum (cream). © Burcu Kepsutlu/HZB
The study shows: After the uptake of nanoparticles into the cell, there are fewer lipid droplets (blue) and multivesicular bodies and instead more mitochondria (green) and endosomes (yellow). © James McNally/HZB
Lipid droplets (blue), containing nanoparticles (orange dots). © HZB
Nanoparticles easily enter into cells. New insights about how they are distributed and what they do there are shown for the first time by high-resolution 3D microscopy images from the lightsources BESSY II and ALBA. For example, certain nanoparticles accumulate preferentially in certain organelles of the cell. This can increase the energy costs in the cell. "The cell looks like it has just run a marathon, apparently, the cell requires 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 enter into the 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, there is still much to be learned about how nanoparticles are distributed in the cells, what they do there, and how these effects depend on their size and coating.
New insights have come from a study at BESSY II, where Prof. Gerd Schneider’s team can take X-ray microscopy images with soft, intensive X-rays. Researchers from the X-ray microscopy group led by HZB biophysicist Dr. James McNally investigated cells with differently coated nanoparticles. The nanoparticles were exactly the same size, but were coated with different active ingredients. Some samples were examined at the MISTRAL beamline at ALBA in Barcelona.
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," emphasizes Schneider. For the first time, the team obtained complete, three-dimensional, high-resolution images of the nanoparticle-treated cells with the organelles contained therein: including lipid droplets, mitochondria, multivesicular bodies and endosomes. Lipid droplets act as energy stores in the cell, while mitochondria metabolize this energy.
Accumulation of nanoparticles
The analysis of the images showed: The nanoparticles accumulate preferentially in a subset of the cell organelles and also change the number of certain organelles at the expense of other organelles. The changes in organelle numbers were similar regardless of the nanoparticle coating, suggesting that many different kinds of nanoparticle coatings may induce a similar effect. To evaluate how general this effect is, further studies with other nanoparticle coatings and with other cell types must be performed.
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," explains McNally. "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," 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 the cell feels like it has just run a marathon."
ACS Nano (2020): Cells Undergo 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
DOI: 10.1021/acsnano.9b09264
- Catalysis research at HZB gets new facilityAs part of the CatLab project, HZB has acquired a unique facility for measuring the catalytic performance of thin-film catalysts. Built by ILS in Adlershof, it has now been delivered. The facility consists of a total of eight chemical reactors in which catalytic systems can be tested. At over €2.5 million, this is the largest single investment in the CatLab project.
- Protein crystallography at BESSY II: faster, better and more and more automaticMany diseases are linked to malfunctions of proteins in the organism. The three-dimensional architecture of these molecules is often highly complex, but it can provide valuable insights into biological processes and the development of drugs. X-ray diffraction at the MX beamlines of BESSY II can be used to decipher the 3D structure of proteins. To date, more than 5000 structures have been solved at the three MX beamlines. Here, we present a review and an outlook with Manfred Weiss, head of the research group for macromolecular crystallography.
- 5000th protein structure at BESSY II: Starting point for a COVID drugMany proteins have a complex architecture that enables biological functions. Molecules can bind to specific sites on a protein and alter its function. A team at HZB has now investigated the Nsp1 protein, which plays a role in infection with the SARS-CoV-2 virus. They analysed protein crystals, previously mixed with molecules from a fragment library, and discovered a total of 21 candidates as starting points for drug development. At the same time, they also decoded the 5000th structure at BESSY II.