A closer look at the communication packages of cells

Cells in our body communicate with each other by sending little balls with protein to one another. Wouter Roos, professor of Molecular Biophysics at the RUG, described as first with colleagues from Amsterdam and Utrecht the mechanical properties of these exosomes from red blood cells, and compared tham to exosomes from cells with a blood condition. ‘It appears that they have very different properties,’ concludes Roos. ‘That offers new possibilities to develop treatments.’ The results have been published in de scientific journal Nature Communications on 23 February.

That cells send little balls with proteins in and out of the cell has been known for a long time. Cells compose those balls using a small part of the cell membrane, the outer wall of the cell. For a long time it was thought that this way cells mainly cleaned up waste from the cell. But for about fifteen years we know that these exosomes are important for the communication between cells. ‘So far we have only studied them in groups to discover their properties. But thanks to a special microscope, we could now study and describe one single exosome,’ says Roos.  

Needle

Roos started the research a few years ago in Amsterdam together with professor in physics and life processes Gijs Wuite and finished it after his arrival in Groningen, where he is now part of the Zernike Institute for Advanced Materials . ‘We have first looked at the red blood exosomes with a touch microscope, the atomic force microscope’ says Roos. ‘This microscope feels over the surface with a needle, so that we discover how the surface looks like.’ A bit like a blind person feels braille letters. ‘We then tested the properties by pressing the small balls with proteins. You then get an idea of the firmness and flexibility of the exosome.’ This way the researchers were the first to map the properties of exosomes from red blood cells.

Surprise

‘Then we looked at red blood cells of people with spherocytosis. People with this condition have far too round and stiff red blood cells. We expected that their vesicles would be harder too. But to our surprise they turned out to be softer.’ That observation led to the insight that especially the soft parts of the cell can form the vesicles. ‘We knew that people with spherocytosis make more vesicles, but that they would show such unexpected behavior, we did not suspect. That insight leads to a lot of new questions, which might help to understand the genesis of the stiff red blood cells in sferocytosis and maybe leads to new therapies.’  

There are still many mysteries left. ‘What exactly is there in such a exosome, for example? What information do they transfer? And how do they know at which cell the information should arrive? Once we know that for healthy cells, we can also better understand how the communication in several diseases. And then we can also develop techniques to better detect those exosomes and make medicines that influence their communication.’

Puzzle

There is an important reason that Roos and others dive into the properties of exosomes. ‘Not only healthy cells communicate with exosomes, but also tumor cells. If we understand them better, we may be able to discover differences between exosomes of healthy cells and exosomes of tumor cells. Then we can use them for diagnostics and to make medicines against cancer,’ explains Roos. In the Netherlands only there are already nine research groups that work on this subject, organized in the Cancer-ID partnership.

D. Vorselen, S. M. van Dommelen, R. Sorkin, M. C. Piontek, J. Schiller, S. T. Döpp, S. A. A. Kooijmans, B. A. van Oirschot, B. A. Versluijs, M. B. Bierings, R. van Wijk, R. M. Schiffelers, G. J. L. Wuite and W. H. Roos : The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis. Nature Communication, DOI: 10.1038/s41467-018-07445-x

Tekst: Christine Dirkse