Biomolecular condensates regulation by interfacial protein clusters

Srabani Roy Chowdhury, MAKAUT

Cellular compartments formed by phase separation in the absence of limiting membranes are considered Biomolecular condensates. In the 1970s, scientists first discovered biomolecular condensates and were known as “granules”. They used electron microscopy to look more closely at the structures in different organisms. P granules are condensates in worms. They are tough and are similar in appearance to sand grains. In 2014, two proteins MEG-3 and PGL-3 were discovered in the P granules. MEG-3 is an intrinsically disordered protein. It was observed that the localized assembly of P granules was controlled by the MEG-3 protein. Viscous liquid droplets are created by PGL-3 whereas MEG-3 makes small clusters and coats the surface of the P granules.

What is Pickering emulsion?

A mixture of liquids that don’t mix properly with each other in general is considered to be an emulsion. Such a mixture that is more stabilized is called a Pickering emulsion. In dairy industries, during the processing of milk, it is pushed through a needle-like pipe. This not only breaks down the fat droplets but also coats them with the casein protein to reduce the surface tension of the droplets. This is done to avoid aggregation of the fat molecules which gets separated from the liquid part of the milk and floats on top. MEG-3 is found to coat the PGL-3 similar to the casein protein that coats fat droplets. It not only keeps the surface tension low and prevents aggregation but also acts as a membrane around the P granules. On glass slides, PGL-3 droplets coated with MEG-3 were observed. They were found to stay evenly separated. There were twice as many droplets than the uncoated condensates that were seen to fuse together, forming lesser and bigger droplets than the coated droplets. Experiments with egg cells of worms that lack MEG-3 showed that the dissolving process of the uncoated P granules is quite slow. This suggests that MEG-3 is responsible for the stabilization of droplets not only under normal conditions but also with changed environmental conditions. Hence, it can be said that MEG-3 is a tool for Pickering emulsions in cells. Later, another enzyme called MBK-3 was identified that works along with MEG-3 and helps in reducing the viscosity of the liquid present inside the P granules.

Conclusion

We know that Pickering emulsion is a very common phenomenon in the food industries but the above observations prove that similar emulsions can happen inside a cell as well and we term it as Pickering-stabilized intracellular emulsion. This explains how the assembling of primordial soup that is present inside cells into compartments to avoid fusing together. Experimental observations show that regulation of condensate dynamics is done by protein clusters that adsorb to the condensate interface.

Also read: Computational biology approaches help accelerate vaccine development

References

• Medicine, J. H. U. S. of. (n.d.). Food science meets cell science in bid to explain inner workings of membrane-free cell compartments. Retrieved September 14, 2021, from https://phys.org/news/2021-09-food-science-cell-membrane-free-compartments.html
• Folkmann, A. W., Putnam, A., Lee, C. F., & Seydoux, G. (2021). Regulation of biomolecular condensates by interfacial protein clusters. Science, 373(6560), 1218–1224. https://doi.org/10.1126/science.abg7071

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