Cells take their ease in turns

A UNIGE team shows that cells that make up our tissues increase in volume when tissues bend. An important discovery for the culture of in vitro organs.

“Sheet” of curved cells in the form of a tube: The cells that were initially organized flat were forced to curl. (c) Aurelien Roux

How do our cells organize themselves to give their final shape to our organs? The answer lies in morphogenesis, the set of mechanisms that regulate their distribution in space during embryonic development. A team from the University of Geneva (UNIGE) has just made a surprising discovery in this area: When a tissue curves, the volume of the cells that make up it increases instead of decreases. This discovery opens new avenues for in vitro organ culture, a partial alternative to animal testing. It also suggests new perspectives for the production of certain materials. This research is published in the journal developmental cell

In biology, the mechanisms that control the distribution of cells in space to shape the shape and structure of our tissues and organs are called “morphogenesis.” These mechanisms are at work during embryonic development and explain how, for example, the folds of our intestines or the alveoli of our lungs are formed. In other words, these phenomena are the basis of our development and that of all living beings.

Cells swell and this is unexpected

In a recent study, Professor Roux’s team examined how the cells that make up a tissue react and adapt when it’s bent. By rolling a monolayer of cells in vitro, a compact, flat collection of cells arranged side by side, the UNIGE scientists made a counterintuitive discovery. “We found that the volume of cells in the curvature increased by about 50% after five minutes instead of decreasing, and then returned to normal within 30 minutes,” explains Aurélien Roux, the last author of this study. This is the opposite of what can be observed when bending an elastic material.

By bending this “sheet” of cells, similar to that of our skin, the researchers more accurately noticed that the latter swelled and took the shape of small domes. “The fact that this volume increase is time-spread and transient also shows that it is an active and living system,” added Caterina Tomba, lead author of the study and former researcher in the Department of Biochemistry at UNIGE. .

A mechanical and biological phenomenon

It is the combination of two phenomena that explains this increase in volume. “The first is a mechanical response to the curvature, the second is linked to the osmotic pressure exerted on the cell,” says Aurélien Roux. The cells evolve in an environment made of salt water. The semi-permeable membrane that separates them from their environment allows water to pass through, but not salt, which exerts a certain pressure on the cell. The greater the salt concentration outside – and thus the so-called osmotic pressure – the more water will pass through the cell membrane, increasing its volume.

“When a curvature is induced, the cells react as if it were the osmotic pressure increasing. As a result, they absorb more water, which causes them to swell,” explains the researcher.

Useful to reduce animal testing

Understanding how cells respond to bending is an important step forward for the in vitro development of organoids. Indeed, these three-dimensional multicellular structures, designed to mimic the micro-anatomy of an organ and its functions, could enable a great deal of research without the need for animal testing. “Our discovery is an active phenomenon that must be taken into account to control the spontaneous growth of organoids, ie to obtain the desired shape and size of the organ,” says Aurélien Roux. The long-term goal would be to be able to ‘culture’ any replacement organ for certain patients.

These results are also interesting for industry. “Today, there are no materials that increase in volume when folded. Engineers conceptualized such a material without ever realizing it, because its production was extremely complicated. Our work therefore also offers new keys to understanding the development of such materials,” concludes Aurélien Roux.

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