How the physics of phase separation helps organize the synapse

What is it about?

The contents of living cells are highly organized. Biomolecules are sorted into various biomolecular condensates as well as membrane-bound organelles. Condensates often assemble through phase separation mechanisms, similar to oil separating from water to stay as two immiscible liquids. At the neuronal synapse, several interesting examples of biomolecular condensates with distinct compositions are located. How these multi-component systems are organized is a crucial unanswered question. In this study, we use inhibitory synapse components to understand the rules governing multi-component biomolecular phase separation. We observe that the phase separation of a scaffolding protein is thermodynamically modulated by the presence of scaffold-binding factors. The degree of perturbation is closely related to the valency and affinity of interactions between two components. We also use a light-activable technology to demonstrate that scaffold condensation can be spatially controlled by the presence of scaffold-binding factors.

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Photo by Rodion Kutsaiev on Unsplash

Photo by Rodion Kutsaiev on Unsplash

Why is it important?

Although biomolecular condensates in cells harbor multiple components, phase separation behaviors are often characterized at the individual molecular level. Our findings deepen the understanding of multi-component phase behaviors, and also suggest that condensation in cells can be spatiotemporally regulated by the scaffolding-binding factors. The insights gained in this study can also be utilized to build and control synthetic condensate systems.