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

Abstract

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.

Viscoelastic phase separation in biological cells

“…In biological cells, this can be achieved by the preferential wetting of the slower phase to the cell wall, nucleus, or membranes 40,41 . Recently, the importance of wetting effects on biological phase separation in cells has been shown 42,43 . For large biomolecular solutions, the interface tension can be very low 44 , which may also impact the phase separation and wetting behaviours 45,46 .…”

“…For example, wetting effects on elastic components, such as cell walls, are crucial for supporting the mechanical stress generated by VPS, as discussed above. For normal liquid-type phase separation, wetting effects affect the domain shape and location of domains formed by phase separation 42,43,80 . In Fig.…”

Endocytosis of Coacervates into Liposomes

“…6 It is thought that wetting is one of the key principles that governs the interaction between droplets and membranes. 7 Recent studies on model systems containing disordered proteins anchored to the surfaces of giant unilamellar vesicles (GUVs) indeed showed that phase separation could induce membrane bending and the assembly of protein-lined membrane tubules. 8 However, it remains unclear how droplet-membrane interactions could be used to direct membrane deformation, and possibly induce endocytosis.…”

Coacervation of poly-electrolytes in the presence of lipid bilayers: mutual alteration of structure and morphology

“…Considering the favorable MARTINI results for poly-E/K coacervates 33 and the general success of the model for describing lipid membranes, 60 we have chosen to use MARTINI v3.0 to study the interaction of poly-E/K with a series of few-component lipid membranes as simple but representative examples of biomolecular condensate/membrane interactions. 17 In particular, we ask the following questions: (i) How does the poly-E/K complex coacervate modulate the membrane structure and morphology? (ii) How does the membrane adsorption (or wetting) modify the structure of the coacervate?…”