A closer look at the communication packages of cells

23 November 2018

Cells in our body communicate with each other by sending little fat balls to one another. Wouter Roos, professor of Molecular Biophysics at the Rijksuniversiteit Groningen, together with colleagues from Amsterdam and Utrecht, is the first to describe the mechanical properties of such fat balls, called exosomes. By studying exosomes of patients with a blood disorder, unexpected results were obtained.

'Exosomes from their blood cells have very different properties than those from healthy individuals,' Roos concludes. 'That offers new possibilities in diagnosis and nanomedicine.' The results have been published in de scientific journal Nature Communications on 23 November.

Wouter Roos SAEYS_NWO_BioPhysics_2017_GT5R1666Wouter Roos Photo credit: Ben Saeys

That cells send little balls, made of fat and 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 cells with these exosomes mainly cleaned up waste from the cell. But for about fifteen years we've known 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.

Playing with a needle

Roos started the research a few years ago in Amsterdam together with professor in physics of life processes Gijs Wuite and finished it after his arrival in Groningen. ‘We  first looked at the red blood cell exosomes with a touch microscope,' says Roos. 'This AFM feels over the surface with a needle, so that we discover what the surface looks like.' A bit like how a blind person feels braille letters. ‘We then tested the mechanical properties by pressing these small fat balls. This provides an idea of the firmness and flexibility of the exosome.’ By doing so, the researchers were the first to map the properties of exosomes from red blood cells.

vesicle and AFM tip credit: Rijksuniversiteit Groningenvesicle and AFM tip Photo credit: Rijksuniversiteit Groningen

Red blood cells

'Next we looked at red blood cells of people with spherocytosis. Patients 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 we never thought that they would show such unexpected behaviour. That insight leads to many new questions, which might help to understand the genesis of the stiff red blood cells in spherocytosis and may lead to new diagnostics.'

Puzzle to solve

There are still many mysteries left. 'What exactly is inside such an exosome, for example? What information do they transfer? And how do they know to which cell they should transfer that information? Once we know this for healthy cells, we can also better understand how the communication in spherocytosis and cancer progresses. And then we can also develop techniques to better detect those exosomes and make medicines that influence their communication.'

Tumour cells

There is an important reason that Roos and others delve into the properties of exosomes. 'Not only healthy cells communicate with exosomes, but also tumour cells. If we understand them better, we may be able to discover differences between exosomes of healthy cells and exosomes of tumour cells. We may then be able to use them in diagnostics and in the development of anti-cancer drugs,' explains Roos. In the Netherlands alone there are nine research groups working on this subject, organised in the Cancer-ID partnership.

Practical information

The article about exosomes is published in Nature Communication with the title "The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis" by 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, DOI: 10.1038/s41467-018-07445-x ’

This research was funded in part by SRON, a NWO Vidi Grant and the STW Cancer-ID partnership.

Source: University of Groningen