Critical capillary waves of biomolecular condensates

Abstract

Biomolecular condensates formed by phase separation are key players in cellular organization, yet their interfacial mechanics remain poorly understood. Here, we show that both synthetic and endogenous nuclear condensates exhibit critical-like interfacial behaviors near the phase boundary, including enhanced capillary fluctuations, critical slowing down, and reduced surface tension. By combining optogenetic control with sub-micron-resolution fluctuation spectroscopy, we quantitatively estimate surface tension, bending rigidity, and effective viscosity. Surface tension diminishes as the system approaches the critical composition, consistent with classical theories of phase separation. Notably, bending elasticity emerges as an unexpected feature of these nuclear liquid-like structures, suggesting the formation of structured interfacial layers that progressively weaken near criticality. Among these condensates, the nucleolus displayed exceptionally high viscosity, which may arise in part from viscoelastic coupling to the surrounding perinucleolar heterochromatin, effectively increasing the apparent viscosity in the long-time fluctuation regime. This non-invasive approach enables probing condensate mechanics in living cells and may provide a basis for diagnosing or modulating condensates in biomedical contexts.