A team from the University of Geneva (UNIGE) has discovered that when tissues curve, the volume of the cells that compose it increases, rather than decreases. The somewhat surprising findings are significant for the study of morphogenesis—the term for the mechanisms that determine the distribution of cells in space to shape the form and structure of our tissues and organs—and opens new avenues for in vitro organ culture as a partial alternative to animal experimentation.
For the study, which was published recently in the journal Developmental Cell, the team investigated how the cells that make up a tissue react and adapt when the tissue is bent. By rolling a monolayer of epithelial cells in vitro, the UNIGE scientists made a counterintuitive discovery. “We found that the volume of cells located in the curvature increased by about 50% after five minutes instead of decreasing, and then returned to normal within 30 minutes,” says Aurélien Roux, with the UNIGE’s Department of Biochemistry. This increased volume is the opposite of what can be observed when bending an elastic material.
The researchers also noticed that the cells swelled to take the shape of small domes. “The fact that this increase in volume is staggered in time and transient also shows that it is an active and living system,” says Caterina Tomba, former researcher in the Department of Biochemistry at the UNIGE.
Two phenomena combine to explain 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,” says 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 concentration of salt outside, the more water will pass through the cell’s membrane, increasing its volume. “When a curvature is induced, the cells react as if it were the osmotic pressure that was increasing. They therefore absorb more water, which has the effect of making them swell,” Roux adds.
Understanding how cells respond to bending is an important advance for the in vitro development of organoids, which are three-dimensional multicellular structures designed to mimic the micro-anatomy of an organ and its functions. Organoids can allow for a great deal of research without the need for animal experimentation. “Our discovery is an active phenomenon to be taken into account in order to control the spontaneous growth of organoids, i.e., to obtain the desired shape and size of the organ,” Roux says. The long-term goal would be to be able to “grow” any replacement organ for certain patients.
The UNIGE results may also be of interest for industrial applications. “Today, there are no materials that increase in volume when folded. Engineers have 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,” Roux adds.