Transient, nano-scale, liquid-like molecular assemblies coming of age

This review examines the dynamic mechanisms underlying cellular signaling, communication, and adhesion via transient, nano-scale, liquid-like molecular assemblies on the plasma membrane (PM). Traditional views posit that stable, solid-like molecular complexes perform these functions. However, advanced imaging reveals that many signaling and scaffolding proteins only briefly reside in these molecular complexes and that micron-scale protein assemblies on the PM, including cell adhesion structures and synapses, are likely made of archipelagoes of nanoliquid protein islands. Borrowing the concept of liquid-liquid phase separation to form micron-scale biocondensates, we propose that these nano-scale oligomers and assemblies are enabled by multiple weak but specific molecular interactions often involving intrinsically disordered regions. The signals from individual nanoliquid signaling complexes would occur as pulses. Single-molecule imaging emerges as a crucial technique for characterizing these transient nanoliquid assemblies on the PM, suggesting a shift toward a model where the fluidity of interactions underpins signal regulation and integration.