Liquid-like condensates that bind actin can polymerize and bundle actin filaments

Liquid-like protein condensates perform diverse physiological functions from the catalysis of biochemical reactions to the assembly of functional biomolecular complexes. Our previous work showed that VASP, a processive actin polymerase, forms condensates that polymerize and bundle actin. Semi-rigid actin filaments polymerized inside condensates, where they partitioned to the inner condensate surface to minimize their curvature. As filaments accumulated at this surface, their collective rigidity overcame the surface tension of the condensate, deforming it into a rod-like shape, filled with a bundle of parallel filaments. These findings suggest a potentially important role for protein condensates in the growth and organization of actin networks. Here we show that this behavior is inherent to all actin-binding condensates and does not require proteins with specific polymerase activity. In particular, we found that condensates composed of Lamellipodin, a protein that binds actin but is not a polymerase, were also capable of polymerizing and bundling actin filaments. One possible explanation is that the condensate environment, which inherently promotes multi-valent protein interactions, allows actin-binding proteins to form multi-valent contacts with actin, facilitating its polymerization. This idea implies that any condensate-forming protein that binds actin could polymerize actin filaments. To test this hypothesis, we added an actin-binding motif to Eps15, a condensate-forming protein that does not normally bind actin. The resulting chimera formed protein condensates that drove efficient actin polymerization and bundling. Collectively, the findings broaden the family of proteins implicated in polymerizing and organizing cytoskeletal filaments to include potentially any protein involved in the assembly or recruitment of cytoskeletal accessory proteins into protein condensates. ### Competing Interest Statement The authors have declared no competing interest.