Cells take their ease in curves

A UNIGE team shows that the cells that make up our tissues increase in volume when the tissues bend. A key discovery for in vitro organ culture.

“Sheet” of curved cells in the shape of a tube: the cells initially organized flat have been forced to roll up. (c) Aurelien Roux

How are our cells organized to give our organs their final shape? 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 field: when a tissue bends, the volume of the cells that compose it increases instead of decreasing. This discovery opens new perspectives 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 Development cell.

In biology, the mechanisms that determine 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 it’s unexpected

In a recent study, Professor Roux’s team investigated how the cells that make up a fabric react and adapt when it is bent. By rolling a monolayer of cells in vitro, which is a compact, flat assembly of cells arranged next to each other, UNIGE scientists have made a counter-intuitive discovery. “We found that the volume of cells located in the curvature increased by about 50% after five minutes instead of decreasing, then returned to normal within 30 minutes”, explains Aurélien Roux, the last author of this study. This is the reverse of what can be observed when bending an elastic material.

By bending this “sheet” of cells, similar to that which makes up our skin, the researchers noticed more precisely that the latter swelled to take the form of small domes. “The fact that this increase in volume is staggered over time and transient also shows that it is an active and living system,” adds Caterina Tomba, first author of the study and former researcher in the Department of Biochemistry of the UNIGE.

A mechanical and biological phenomenon

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

“When curvature is induced, cells react as if osmotic pressure is increasing. They therefore absorb more water, which has the effect of making them swell,” explains the researcher.

Useful for reducing animal testing

Understanding how cells respond to bending is an important advance for the in vitro organoid development. These three-dimensional multicellular structures, designed to mimic the micro-anatomy of an organ and its functions, can in fact allow a great deal of research without resorting to animal experimentation. “Our discovery is an active phenomenon to be taken into account in order to control the spontaneous growth of organoids, in other words to obtain the desired shape and size of the organ”, specifies Aurélien Roux. The long-term goal would be to be able to “grow” any replacement organ for some patients.

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

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