What influences such pattern formations has long been a source of mystery, but scientists from the University of Bristol and Saarland University in Germany, have shown the answer may lie within – in human red blood cells. Their findings could lead to better diagnostics for blood disorders.
The research, published today in the journal PNAS, reveals the stripe patterns which appear when red blood cells are separated in a centrifuge are primarily caused by the cells' own attraction and adhesion to neighbouring cells, contrary to previous belief.
Co-lead author Dr Alexis Darras, Lecturer in Physics at the University of Bristol, said: "It was previously assumed these patterns occurred due to the irregular ageing process and associated water loss of red blood cells during the red blood cell lifespan of around three months.
'But our study challenges this and confirms that the real cause is not water loss, it's cell aggregation. It's a remarkable discovery, which could have far-reaching applications."
When red blood cells are centrifuged in a solution that gets gradually heavier from top to bottom, an irregular pattern appears: the cells gather in red 'stripes' from top to bottom, with white stripes in between where fewer red blood cells are found.
Dr Darras explained: "Younger blood cells, which have just formed, contain more water; older cells contain less. Older cells therefore have a higher density because the remaining hemoglobin is heavier than water. So older cells settle at the bottom during centrifugation, while younger ones accumulate at the top as they are lower density and lighter."
In experiments, the physicists mixed red blood cells into a medium of water, salts, and nanoparticles and centrifuged them.
Co-lead author Felix Maurer, a PhD student at Saarland University said: "Like weather balloons in Earth's thinning atmosphere, red blood cells distribute so that each cell remains at an equilibrium height – the point where its average density equals that of the surrounding medium."
Findings showed that stripe formation was driven by the sheer number of cells.
"The pattern only emerges through the interaction of very many cells. In our experiment, about one billion cells were in a single tube. When the number of cells was reduced, we observed completely different behaviour," Felix added.
"Without aggregation, i.e. cells sticking together, the cells distribute evenly, and no stripes form."
This means the typical stripe pattern is only formed due to many cells clustering in a confined space combined with the pull of gravity.
These new insights could pave the way for new diagnostic approaches to blood disorders, such as sickle cell anemia, where cells deform and their flow and clustering behaviour changes.
Co-lead author Christian Wagner, Professor of Physics at Saarland University, said: "In sickle cell anemia, for example, a different stripe pattern appears and until now, no one could explain why."
Another part of the study addresses how patterns and structures arise in nature. To explore and ultimately explain this, the physicists created a mathematical model based on the so-called Dynamic Density Functional Theory, which is a way to predict how particles move and arrange themselves over time based on their interactions and the space around them.
Prof Wagner said: "A similar equation to the one we developed also describes zebra stripes, bird flocks, and fingerprints. In our case, short-range interactions between individual cells lead to a preferred stripe width and spacing.
"Bird flocks also exhibit collective behaviour, forming patterns based on simple neighborhood rules. A similar idea applies to fingerprint formations. It's amazing to think that specific observations of blood cells in the lab help us better understand fundamental laws of nature."
Paper
'Competing aggregation and iso-density equilibrium lead to band pattern formation in density gradients' by F. Maurer et al. in PNAS
