Applicability of phase coexistence to small, out-of-equilibrium cells

Establish whether the concept of phase coexistence, which is unambiguously defined in thermodynamically large equilibrium systems, accurately applies to biomolecular condensation within small, living cells operating out of equilibrium.

Background

The paper cautions against directly equating cellular condensates with equilibrium phase separation, noting that phase coexistence is rigorously defined only in large systems at equilibrium. Because cells are small and maintain nonequilibrium conditions, it is uncertain whether phase coexistence descriptions are strictly valid in cellular contexts.

Resolving this question would determine the appropriate physical framework for modeling condensation in vivo and guide interpretation of experimental observations that rely on phase-separation analogies.