A change in rigidity switches the function of protein condensates involved in sensing touch
Researchers at IRB Barcelona, based in the Barcelona Science Park, and ICFO describe in Nature Cell Biology the mechanism by which the MEC-2 protein condensates of touch receptor neurons transition from fluid to solid-like states, switching their role in the transmission of mechanical forces. These findings pave the way for developing innovative therapies and treatments.
Touch plays a fundamental role in our physical, emotional, and social well-being. From a primary way of conveying emotions to sensory integration, it is crucial for the complex growth of cognitive, emotional, social, and behavioural abilities, especially during the early development of infants and children. Touch allows us to build connections with others, eases pain and stress, and helps us to understand the world around us, providing us with crucial information such as the texture, temperature, and shape of objects.
When sensing any stimuli, such as when the body is being touched, the mechanical signals are transformed into biological responses that help us to adapt to continuously changing environments. This transformation involves a variety of intracellular and molecular processes inside the cells that enable us to perceive and respond to tactile stimuli effectively, converting the physical stimuli into electrical activity. The capacity of cells to sense and transmit mechanical forces depends on the correct assembly, localization, and mechanical properties of the protein complexes in the force transmission pathway. Often, large macromolecular protein complexes form liquid-like condensates in a process akin to phase separation.
Such biomolecular condensates are found in many, if not all, eukaryotic cells, and they play a vital role in various physiological and pathological processes, thus emerging as a promising clinical target. Given the liquid-like nature of these biomolecular condensates, their role in mechanotransduction, that is, any mechanism by which cells convert mechanical stimulus into electrochemical activity, is not clear. Although studies have shown that their material properties can change from liquid to solid over time, there is one remaining question: Can these condensates, with different material properties, have different biological functions?
Examining MEC-2 protein condensates in touch receptor neurons
To address the question, ICFO researchers Drs. Neus Sanfeliu, Frederic Català, Iris Ruider, Montserrat Porta and Stefan Wieser, led by Prof. Michael Krieg, in collaboration with IRB Barcelona researchers Drs. Borja Mateos, Carla Garcia, Maria Ribera and Adrià Canals, led by ICREA Prof. Xavier Salvatella, have published a study in Nature Cell Biology identifying the mechanism by which specific protein condensates transition from liquid to solid states, enabling the stability and transmission of the mechanical forces.
The focus of the study was the MEC-2 protein member of the Stomatin family, which is essential for the membrane mechanics and modulation of the ion channel activity. Sanfeliu and the team found that MEC-2 also forms condensates in the touch receptor neurons of the roundworm Caenorhabditis elegans, a model organism widely used for studying the structure and function of the nervous system.
Given the significant roles that biological condensates play in various physiological and pathological processes, a better understanding of their functions might open up new opportunities for innovative therapies and treatments, such as those aimed at understanding the molecular details that drive rigidity transitions in health and disease.
“We are really excited about the role of condensate maturation in mechanotransduction,” says ICFO Prof. Michael Krieg, “and about looking for ways to investigate how defects in protein condensation participate in the development of neurological disorders.“
Dr. Xavier Salvatella concludes, “It has been known for some time that changes in the material properties of condensates can be detrimental and lead to diseases. But this work shows how they can also be functional and be regulated by protein-protein interactions. It has been great to contribute to this discovery and we look forward to continuing to work on this together with our colleagues at ICFO”.
This study exemplifies the successful collaboration between the research groups involved. As Dr. Krieg says, “We look forward to continued collaboration with Dr. Salvatella’s research group at IRB Barcelona in the hopes of finding new amazing results that can further help us understand cell mechanical properties at the molecular and systems level, to tackle health and disease issues.”
» Link to the news: IRB Barcelona website [+]
» Reference article: A rigidity phase transition of Stomatin condensates governs a switch from transport to mechanotransduction.Neus Sanfeliu-Cerdán, Frederic Català-Castro, Borja Mateos, Carla Garcia-Cabau, Maria Ribera, Iris Ruider, Montserrat Porta-de-la-Riva, Adrià Canals-Calderón, Stefan Wieser, Xavier Salvatella & Michael Krieg Nature Cell Biology (2023) DOI: 10.1038/s41556-023-01247-0