How does the collective interplay of many individual cells give rise to a perfectly shaped organism? This question lies at the heart of a new study published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS, USA). An international research team involving Bielefeld University has investigated how cells, despite heterogeneous protein production, work together to create an ordered structure outside themselves: the extracellular matrix (ECM).

“By visualizing an important structural protein, we were able to uncover principles of self-organization in a living organism,” explains Professor Dr Armin Hallmann from Bielefeld University, senior author of the study. The researchers worked with the green alga Volvox carteri, a spherical, multicellular model organism consisting of about 2,000 cells.

Visualized: The ECM of a Living Organism
The extracellular matrix is a mesh-like material secreted by cells. It provides structure to tissues, transmits signals, and plays a central role in the development of multicellular organisms, including humans, for instance in skin, cartilage, or the brain.
In the study, the ECM protein pherophorin II was genetically tagged with a fluorescent marker originally derived from a jellyfish. This enabled the fine structure of the ECM in the living organism to be visualized at high resolution using a confocal laser scanning microscope (CLSM).

The results show that pherophorin II is located at the boundary structures of the ECM, where ECM compartments of individual cells meet, as well as on the organism’s surface. Although each cell contributes varying amounts of proteins to the ECM, the organism’s outer structure remains stable and spherical.

Ordered Structure Despite High Variability of Cells
The scientists discovered that the surface area of ECM compartments follows a mathematical k-gamma distribution, indicating large fluctuations in protein production between individual cells. No single cell controls the formation of the ECM. Instead, many cells contribute simultaneously, so to speak, by remote control, since the ECM is formed outside the cells. “It’s like many people building a puzzle together while blindfolded, and it still works,” says Hallmann.
The ECM structure that forms around the cells develops rounded or polygonal boundaries that dynamically evolve as the organism grows, making the geometry resemble that of a foam.
These findings provide new insights into developmental biology: How do cells manage to collectively generate external structures without direct coordination? The answer seems to lie in self-organization, an interplay of biological, physical, and mathematical processes.

The study was carried out in close collaboration between the Department of Cell and Developmental Biology of Plants at Bielefeld University and the Department of Applied Mathematics and Theoretical Physics (DAMTP) at the University of Cambridge. Alongside Prof. Hallmann, the research team included Dr Benjamin von der Heyde and Dr Eva Laura von der Heyde (Bielefeld University) as well as Anand Srinivasan, Dr Sumit Kumar Birwa, Dr Steph Höhn, and Prof. Raymond Goldstein (Cambridge).

Professor Raymond Goldstein emphasizes: “This work demonstrates the powerful synergy that emerges when biologists, physicists, and mathematicians work together to unravel the mysteries of life.” The research was funded in part by the Wellcome Trust and the John Templeton Foundation.