New study on an unprecedented mechanism for cellular membrane remodelling by the Agudo-Canalejo lab

The study was led by cell biologist Dr Xiaofeng Fang in the School of Life Sciences of Tsinghua University and biophysicist Dr Roland Knorr in the Center for Biochemistry of the University of Cologne on the experimental side, by mathematician Dr Sebastian Aland in the Faculty of Mathematics and Computer Science of the TU Bergakademie Freiberg on the computational side, and by physicist Dr Jaime Agudo-Canalejo in the Biophysics Group of UCL’s Department of Physics and Astronomy on the theoretical side.

The cell interior is made up of many compartments, separated by membranes. To remodel these compartments, membranes often need to be cut into pieces, a process that was until now thought to be mediated exclusively by specialized “scission” proteins. The team has shown that there exists an additional, much simpler mechanism for membrane scission, mediated by droplet-like objects called biomolecular condensates.

In particular, specialized scission proteins need to be powered by a chemical fuel, which in the biological context is provided by ATP molecules. The condensate-mediated mechanism now uncovered, on the other hand, is ATP-independent and mediated by purely physical interactions. This new mechanism was observed in plant cells by Dr Fang’s group, and could be recapitulated in an in vitro system using a minimal number of ingredients by Dr. Knorr’s group.

Dr Agudo-Canalejo, who developed a theoretical model to understand the new mechanism, describes it as follows: “Just like water droplets wetting a glass surface, biomolecular condensates can wet cellular membranes. However, because cellular membranes are highly flexible, they can bend and wrap around the condensate until they fully enclose it. Most surprisingly, condensates can go all the way, by ultimately pinching off the neck that connects the membrane-wrapped condensate to the rest of the membrane.”

The team showed that these scissor condensates also operate in mammalian cells, where they can step in if specialized proteins are missing or malfunctioning, acting as a failsafe. It is therefore conceivable that scissor condensates play an important role in medically relevant processes. Autophagy, for example, is an intracellular recycling process important in ageing, in cancer and in immune responses. The team is now working on understanding which scissor condensates influence autophagy. Additionally, because of the mechanism’s simplicity, the team speculates that scission condensates may have been the main actors of membrane scission in the early stages of cellular evolution, before specialized scission proteins evolved.

Dr Agudo-Canalejo’s work was supported by the German Research Foundation.

Links

• Research article in Nature
• Dr Jaime Agudo-Canalejo’s academic profile
• UCL Physics & Astronomy  
• UCL Institute for the Physics of Living Systems

Image

• Left: standard mechanisms for membrane remodelling are mediated by complicated protein machinery, such as the ESCRT family of proteins, which requires energy input.
• Right: the new mechanism requires a single component, FREE1, which forms droplet-like biomolecular condensates that (i) wet and deform and (ii) finally scission the membrane, without any energy input.