Nonequilibrium Liquid-Liquid Phase Separation: A Physical Pathway to the Emergence of Multicellularity

The emergence of complex multicellularity marks one of life’s key evolutionary transitions. By understanding the physical constraints that cells face during this transition, we can gain critical insights into this evolutionary milestone, which also holds promise for advancements in regenerative medicine and engineered biomaterials. To investigate this transition, we study the reaggregation process in sponges, where dissociated cells from a mature sponge coalesce and redifferentiate to form a new, functional sponge. Although this remarkable phenomenon has been observed since 1907, prior work has predominately focused on the molecular, genetic, and ecological aspects.

Here, we introduce new experiments that highlight the role of nonequilibrium physics in sponge aggregation, revealing hallmarks of liquid-liquid phase separation. We identify the coarsening process during aggregation and quantify how this behavior scales with time over the aggregation process. We connect our observations to theoretical frameworks developed to describe phase separation in active liquids, investigating the impact of key control parameters on the dynamics of aggregation. Our results show that the macroscale behavior of sponge reaggregation can be understood through the lens of nonequilibrium physical processes driven by the microscopic interactions of active agents, paving the way for a physics-based general model of multicellular emergence.