Listening to each other
Like all complex organisms, every human originates from a single cell that multiplies through countless cell divisions. Thousands of cells coordinate, move and exert mechanical forces on each other as an embryo takes shape. Researchers at the Göttingen Campus Institute for Dynamics of Biological Networks (CIDBN), the Max Planck Institute for Dynamics and Self-Organisation, and the University of Marburg have now discovered a new way that embryonic cells coordinate their behaviour. This involves molecular mechanisms previously known only from the process of hearing. The researchers attribute the fact that such different cells use the same proteins for two such different functions to their evolutionary origin. The results were published in Current Biology.
The organism used to investigate embryonic development:The image shows a top-down view of a fruit fly embryo. In the areas coloured red, cells synchronise their mechanical pulling force. / Photo: A. R. Choudhury, M. Häring
Bernstein member involved: Fred Wolf
The interdisciplinary research team used an unusual combination of methods from developmental genetics, brain research, hearing research and theoretical physics to make a surprising discovery in cell communication: they found that in thin layers of skin, cells register the movements of their neighbouring cells and synchronise their own tiny movements with those of the others. Groups of neighbouring cells thus pull together with greater force. Thanks to their high sensitivity, the cells coordinate very quickly and flexibly as these subtle forces are the fastest signals travelling across embryonic tissue. When the cells were genetically deprived of their ability to “listen” to each other, the entire tissue changed and development was delayed or failed altogether.
The researchers integrated cellular coordination into computer models of the tissue . These models showed that the “whispering” among neighbouring cells leads to an interwoven choreography of the entire tissue and protects it from external forces. Both effects were confirmed by video recordings of embryonic development and further experiments. “Using AI methods and computer-assisted analysis, we were able to examine about a hundred times more cell pairs than was previously possible in this field,” explains Dr Matthias Häring, group leader at the CIDBN and co-author of the study. “This big data approach gives our results the high level of accuracy needed to reliably get to the bottom of these delicate interactions between cells.”
The mechanisms revealed here in embryonic development were already known to play a role in the process of hearing. For instance, when very quiet sounds are heard, the hair cells in the ear, which convert sound waves into nerve signals, react to tiny mechanical movements. At the threshold of hearing, the cell protrusions bend over distances of only a few atomic diameters. The ear is so sensitive because of special proteins that convert mechanical forces into electrical currents. Until now, almost no one suspected that such sensors of force also play an important role in embryonic development. In principle, this is possible because every cell in the body carries the genetic blueprints for all proteins and may use them as needed.
The phenomenon could also provide insights into how the perception of force at a cellular level has evolved. “The evolutionary origin of these force-sensitive ion channel proteins probably lies in our single-celled ancestors, that we share with fungi and which emerged long before the origin of animal life,” explains Professor Fred Wolf, Director of the CIDBN and co-author of the study. “But it was only with the evolution of the first animals that the current diversity of this protein type emerged.” Future work should determine whether the original function of these cellular “nanomachines” was to perceive forces inside the body rather than, as in hearing, to perceive the outside world.
