Biomolecular condensates—cellular compartments formed through phase separation—play essential roles in organizing the interior of cells without membranes. These dynamic structures help regulate processes such as gene expression and RNA metabolism, and their dysfunction has been linked to disease. Despite their importance, the physical properties governing how condensates form, change, and interact with their surroundings remain poorly understood.

To precisely control when and where condensates form, the researchers used the Corelet system—an optogenetic platform that enables light-controlled condensate formation in living cells. The team combined this approach with high-resolution imaging and fluctuation spectroscopy—a technique that analyzes tiny, naturally occurring movements at droplet surfaces—thereby enabling systematic examination of condensate behavior under different conditions. By tracking subtle shape fluctuations over time, the researchers extracted key mechanical features. Their analysis revealed that condensates are governed not only by surface tension, which keeps droplets smooth and spherical, but also by an unexpected form of interfacial elasticity. This finding suggests that condensate boundaries are more structured than previously thought, potentially due to the organization of specific molecules at their surfaces.

The study also compared different types of condensates found in the cell nucleus, including nucleoli and nuclear speckles. While these structures share common physical features, they showed notable differences in how they flow and respond to deformation. In particular, the nucleolus behaved as a much more viscous and complex material, likely reflecting its dense internal organization and interactions with surrounding chromatin. These findings highlight how the cellular environment can strongly influence condensate behavior.

A central discovery of this work is that condensates exhibit behavior similar to systems near a critical phase boundary. As conditions approach this boundary, the interface between condensed and surrounding phases becomes increasingly dynamic, with larger, more pronounced fluctuations. At the same time, the forces that typically stabilize the droplet surface weaken. This behavior aligns with classical theories of phase transitions and suggests that criticality may be a general feature of biomolecular condensates in living cells.

Importantly, these patterns were observed not only in engineered systems like Corelets but also in natural cellular structures, indicating that the same underlying physical principles apply across biological contexts. This unifying insight provides a new framework for understanding how condensates form and function under physiological conditions.

Taken together, this study establishes a powerful approach for directly measuring the physical properties of condensates in living cells. By revealing how surface tension, elasticity, and viscosity work together—and how these properties change near critical points—it offers a deeper understanding of the physical basis of intracellular organization. These insights may ultimately help guide new strategies for diagnosing or controlling abnormal condensate behavior associated with disease.

• doi: 10.1103/8rgq-wymv