Cells, boundaries, and the emergence of biological order | EMBL

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Shreya Ghosh

30 June 2026

Science & Technology

Cells, boundaries, and the emergence of biological order

Scientists have shown how the edges of biological tissues create geometric constraints that help cells position themselves in a magnet-like manner, giving rise to structure and order inside developing embryos

Polarised cells in the developing epiblast (seen here in blue) orient themselves in structured patterns as modelled on the right, depending on their interactions with different kinds of tissue boundaries. Credit: Takafumi Ichikawa, Pamela Guruciaga, Anna Erzberger, Creative Team/EMBL

Summary

During embryonic development, cells with biochemically distinct ends – called polarised cells – organise into distinct patterns based on their orientation.

Using theoretical physics approaches and quantitative experiments, scientists have shown how the shape of tissue boundaries determines these patterns.

They found that specific features in these patterns – called topological defects – determine where the proamniotic cavity, an important structure for embryonic development, forms.

This research identifies fundamental principles that govern how order and functional structures emerge inside complex biological systems.

One of the most striking biological transitions in nature happens early in development, when an embryo transforms from a simple ball of cells into a highly ordered structure with distinct tissue layers that later develop into various organ systems. If one imagines the cells of an embryo as people, it is as if a disorderly crowd resolves spontaneously into neat rows and columns.

New research by EMBL researchers and their collaborators uses a combination of theoretical physics and experimental biology to show how this process arises from interactions between tissue geometry and the directional properties of cells. The results were published recently in companion publications in the journals Nature Physics and Nature Materials.

The studies resulted from a collaboration between Anna Erzberger’s group at EMBL Heidelberg and Takafumi Ichikawa at Kyoto University, Japan, together with scientists at the Hubrecht Institute, Netherlands. Their goal was to understand how order emerges in complex biological systems.

When cells behave like tiny magnets

Pamela Guruciaga, a postdoc in the Erzberger Group, has long been interested in understanding how order develops in interaction with the environment. A physicist by training, she was struck by the similarities between the properties of certain biological systems and the magnetic systems she studied during her PhD.

Certain cells are distinctly polarised – they have two ends that are very different from each other. In this, they resemble tiny magnets, which have north and south poles. In an early-stage mouse embryo, cells of the epiblast – which eventually give rise to all the major tissues – behave in this manner. These cells have an apical and a basal end, characterised by different compositions and concentrations of various biological molecules.

The team decided to investigate the fundamental principles governing the behaviour of systems where such polarised cells are present in bulk and face physical constraints at the tissue borders.

For example, imagine if people inside a crowded room were given certain rules as to which way they could face relative to the walls and floor and used this to orient themselves in relation to one another. Guruciaga and her colleagues wanted to figure out what these rules were for epiblast cells.

By focusing on how the cellular orientations interact with each other and their environment, the researchers built a minimal model that predicts how organisation changes when these interactions are altered.

To test their predictions, the team relied on experimental measurements led by Ichikawa, a researcher at Kyoto University, who began this collaboration as a postdoc in the lab of Takashi Hiiragi at EMBL (now a Group Leader at the Hubrecht Institute and a Visiting Professor at Kyoto University). While they were at EMBL, Ichikawa and colleagues had developed an ex vivo embryo culture system that allowed scientists to make precise three-dimensional measurements and see the effects of perturbations.

“It was a very synergetic and fun collaboration across time zones,” said Guruciaga. “For me, as a physicist, I may know why something works, but it’s still kind of magic to see that it’s all true in messy biological systems. It was also super interesting coming from a pure physics perspective to come up with a common language to work with biologists.”

On (topological) defects and development

The team observed experimentally that in the cup-shaped epiblast, different boundaries resulted in different orientations for epiblast cells. When the boundary was lined with the extracellular matrix – the three-dimensional network of proteins that surrounds some...