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Deciphering cell language

Deciphering cell language
Deciphering cell language

Understanding the language of cells in order to redirect them where it is necessary. This is one of the possibilities unveiled by the researchers of the Center for Regenerative Medicine of Barcelona (CMR[B]), led by Dr. Samuel Ojosnegros, who managed to describe in their latest paper the intercellular communications mechanism involved in cell relocation. The work, published by the prestigious journal Proceedings of the National Academy of Sciences (PNAS), was carried out in collaboration with the groups of Elena Martínez (IBEC) and Melike Lakadamyali (ICFO), among others.

"We wanted to understand this communications system, which is very sophisticated, as much in detail as possible. Although we already knew the agents involved, until now we did not have the tools to decipher the language, that is, their operating mechanism”, says Samuel Ojosnegros, first author of the study. To study the messages sent by cells, in a joint effort between institutes of Barcelona and California, the authors have developed a new microscopy technique that allows observing the communication signals in living cells. This technique is capable of showing protein aggregation at the sub-pixel level, which is represented by a colour scale, and allows recording real-time sequences of how a cell responds to a specific stimulus at high resolution.

This communications system is used by cells as a kind of internal GPS to reach their destination in the organs during embryonic development, the regeneration of stem cells and during the metastasis of invasive tumours.

One of the current limitations of regenerative medicine is the difficulty of ensuring that the stem cells that are transplanted to a patient reach and position themselves in the desired destination. "Once this mechanism is described, we can take the first steps in order to be able to manipulate it to steer stem cells much more efficiently, since it is the system they naturally use”, says the CMR[B] researcher.

Condensation versus polymerization

Cell communication is a precisely orchestrated process based on the existence of membrane receptor proteins that are capable of capturing external signals from the environment and translating them internally. In the study, the CMR[B] team focused on Eph membrane receptors and their ligand ephrin.

"Thanks to our microscopy techniques, we were able to observed that the Eph receptor, in the presence of ephrin, begins to aggregate creating large structures. This aggregation is not homogeneous, but follows two differentiated patterns, which we have called polymerization (monomer clustering) and condensation (oligomer clustering). The balance between these two processes regulates the dynamic range of response, because although polymerization involves the activation of the monomers, in condensation the cluster is absorbed by the cell, thus cutting the signal”, explains Dr. Ojosnegros.

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Eph-ephrin signaling modulated by polymerization and condensation of receptors

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