Macromolecular condensation is unlikely to buffer intracellular osmolality

Watson et al . (2023, Macromolecular condensation buffers intracellular water potential, Nature 623: 842-852) have proposed that the reversible formation and disassembly of molecular condensates could act as the primary buffer of cytoplasmic osmolality in the face of changes in extracellular osmolality. In this communication, I show using well-established membrane biophysics, that the water permeability of plasma membranes is likely to overwhelm any cytoplasmic water buffers.