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.