Communication is the key, also between cells.
Just as we use Google Maps, cells rely on gradient sensing of signal molecules to reach their destination. However, in their case, the destination is the source of the attractant and not the restaurant of choice. Using mathematical models, researchers from Helmholtz Munich found that cellular communication and geometry can significantly affect the ability of groups of cells to measure gradients. Their findings were published in the open-access journal PLOS Computational Biology.
Cell migration is crucial for the development and “maintenance” of our bodies. For example, it occurs in normal conditions during embryogenesis, organogenesis, and angiogenesis. However, it also takes place in pathogenic events, such as wound healing after tissue injury, immune responses, and cancer metastases. Migration can occur in response to a gradient of signaling molecules, and cells can improve their ability to measure gradients by clustering together and communicating. Jonathan Fiorentino, a previous postdoc at the Institute for Epigenetics and Stem Cells, and his group leader Antonio Scialdone have now shown that the size, the geometry, and the type of communication in groups of epithelial cells affect gradient sensing ability.
The art of cellular communication is the language of gradient sensing.
To do that, the researchers used a mathematical model for collective gradient sensing via intercellular communication. The model posits the existence of two reporter molecules produced in response to the external signal: a local reporter that stays in the cell and a global reporter that is exchanged between cells. Each cell can then measure the gradient by combining the information included in the local and the global reporter levels. The researchers extended this model to consider two-dimensional systems of epithelial cells, estimating how cellular shape and long- versus short-range cellular communication affect gradient sensing ability.
“We found that with weak, short-range cellular communication, small groups of cells can measure gradients with higher precision, whereas in the case of long-range communication having more cells with irregular geometries gives an advantage”, explained Jonathan Fiorentino, the first author of the publication. This could explain why some migration events in epithelia are accompanied by extensive cell rearrangements that change cellular geometries.
“Using our mathematical framework, we can analyze any specific cellular geometry and tissue size and find which type of cellular communication is more effective to measure signaling gradients. This will help identify the mechanisms of cellular communication in different contexts and predict the properties of the molecules that mediate the communication”, said Antonio Scialdone, who led the study.
The modeling framework is publicly available to the community on Github.
About the people
Jonathan Fiorentino and Antonio Scialdone are part of the Institute for Epigenetics and Stem Cells, the Institute of Functional Epigenetics, and the Institute of Computational Biology at Helmholtz Munich.
Fiorentino, J., & Scialdone, A. (2022). The role of cell geometry and cell-cell communication in gradient sensing. PLOS Comp Bio. PMID: 35286298.