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Abstract:
Biomolecular condensates are small droplets forming spontaneously in
biological cells through phase separation. They play a role in many cellular
processes, but it is unclear how cells control them. Cellular regulation often
relies on post-translational modifications of proteins. For biomolecular condensates, such chemical modifications could alter the molecular interaction
of key condensate components. Here, we test this idea using a theoretical
model based on non-equilibrium thermodynamics. In particular, we describe
the chemical reactions using transition-state theory, which accounts for the
non-ideality of phase separation. We identify that fast control, as in cell signalling, is only possible when external energy input drives the reaction out of
equilibrium. If this reaction differs inside and outside the droplet, it is even
possible to control droplet sizes. Such an imbalance in the reaction could be
created by enzymes localizing to the droplet. Since this situation is typical
inside cells, we speculate that our proposed mechanism is used to stabilize
multiple droplets with independently controlled size and count. Our model
provides a novel and thermodynamically consistent framework for describing
droplets subject to non-equilibrium chemical reactions.
