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Significance The uptake of molecules into cells, known as endocytosis, requires membrane invagination and the formation of vesicles. A version of endocytosis that is independent of actin polymerization is aided by the assembly of membraneless biomolecular condensates at the site of membrane invagination. Here, we show that endocytic condensates are viscoelastic bodies that concentrate key proteins with prion-like domains to enable membrane remodeling. A distinct molecular grammar, namely the preference for glutamine versus asparagine residues, underlies the cohesive interactions that give rise to endocytic condensates. We incorporate material properties inferred using active rheology into a mechanical model to explain how cohesive interactions within condensates and interfacial tensions among condensates, membranes, and the cytosol can drive membrane invagination to initiate endocyosis.

Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling