Intracellular wetting mediates contacts between liquid compartments and membrane-bound organelles

Protein-rich droplets, such as stress granules, P-bodies, and the nucleolus, perform diverse and specialized cellular functions. Recent evidence has shown the droplets, which are also known as biomolecular condensates or membrane-less compartments, form by phase separation. Many droplets also contact membrane-bound organelles, thereby functioning in development, intracellular degradation, and organization. These underappreciated interactions have major implications for our fundamental understanding of cells. Starting with a brief introduction to wetting phenomena, we summarize recent progress in the emerging field of droplet-membrane contact. We describe the physical mechanism of droplet-membrane interactions, discuss how these interactions remodel droplets and membranes, and introduce membrane scaffolding by liquids as a novel reshaping mechanism, thereby demonstrating that droplet-membrane interactions are elastic wetting phenomena. Membrane-less and membrane-bound condensates likely represent distinct wetting states that together link phase separation with mechanosensitivity and explain key structures observed during embryogenesis, during autophagy, and at synapses. We therefore contend that droplet wetting on membranes provides a robust and intricate means of intracellular organization.

Automated summary

Protein-rich droplets, formed by phase separation and interacting with membrane-bound organelles, play crucial roles in intracellular organization and function. The physical mechanisms of droplet-membrane interactions and the novel reshaping mechanism of membrane scaffolding by liquids provide insights into the complex and elastic wetting phenomena in cells. These interactions link phase separation with mechanosensitivity and explain key cellular structures observed during embryogenesis, autophagy, and at synapses.