Researchers have captured the first clear view of the hidden architecture that helps shape a simple multicellular organism, showing how cells work together to build complex life forms.
In a study published in the journal Proceedings of the National Academy of Sciences (PNAS), a team of British and German scientists revealed the structure of the extracellular matrix in Volvox carteri, a type of green algae that is often used to study how multicellular organisms evolved from single-celled ancestors.
The extracellular matrix (ECM) is a scaffold-like material that surrounds cells, providing physical support, influencing shape, and playing an important role in development and signalling. Found in animals, plants, fungi and algae, it also played a vital part in the transition from unicellular to multicellular life.
Because the ECM exists outside the cells that produce it, scientists believe it forms through self-assembly: a process still not fully understood, even in the simplest organisms.
To investigate, researchers at the University of Bielefeld genetically engineered a strain of Volvox in which a key ECM protein called pherophorin II was made fluorescent so the matrix’s structure could be clearly seen under a microscope.
What they saw was an intricate foam-like network of rounded compartments that wrapped around each of Volvox’s roughly 2,000 somatic, or non-reproductive, cells.
Working with mathematicians at the University of Cambridge, the team used machine learning to quantify the geometry of these compartments. The data revealed a stochastic, or randomly influenced, growth pattern that shares similarities with the way foams expand when hydrated.
These shapes followed a statistical pattern that also appears in materials like grains and emulsions, and in biological tissues. The findings suggest that while individual cells produce ECM proteins at uneven rates, the overall organism maintains a regular, spherical form.
That coexistence – between noisy behaviour at the level of single cells and precise geometry at the level of the whole organism – raises new questions about how multicellular life manages to build reliable forms from unreliable parts.
“Our results provide quantitative information relating to a fundamental question in developmental biology: how do cells make structures external to themselves in a robust and accurate manner,” said Professor Raymond E Goldstein from Cambridge’s Department of Applied Mathematics and Theoretical Physics, who co-led the research. “It also shows the exciting results we can achieve when biologists, physicists and mathematicians work together on understanding the mysteries of life.”
“By tracking a single structural protein, we gained insight into the principles behind the self-organisation of the extracellular matrix,” said Professor Armin Hallmann from the University of Bielefeld, who co-led the research. “Its geometry gives us a meaningful readout of how the organism develops as it grows.”
The research was carried out by postdoctoral researchers Dr Benjamin von der Heyde and Dr Eva Laura von der Heyde and Hallmann in Bielefeld, working with Cambridge PhD student Anand Srinivasan, postdoctoral researcher Dr Sumit Kumar Birwa, Senior Research Associate Dr Steph Höhn and Goldstein, the Alan Turing Professor of Complex Physical Systems in Cambridge’s Department of Applied Mathematics and Theoretical Physics.
The project was supported in part by Wellcome and the John Templeton Foundation. Raymond Goldstein is a Fellow of Churchill College, Cambridge.
Reference:
B von der Heyde, A Srinivasan et al. ‘Spatiotemporal distribution of the glycoprotein pherophorin II reveals stochastic geometry of the growing ECM of Volvox carteri,’ Proceedings of the National Academy of Science (2025). DOI: 10.1073/pnas.2425759122