Kinetic trapping organizes actin filaments within liquid-like protein droplets

• Published in: Nature communications Vol. 15; no. 1; p. 3139
• Main Authors: Chandrasekaran, Aravind, Graham, Kristin, Stachowiak, Jeanne C., Rangamani, Padmini
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-04-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 119/118; 631/57/2266; 631/57/2272/1590; 631/80/128/1276; Actin; Bundling; Condensates; Deformation; Droplets; Filaments; Humanities and Social Sciences; Kinases; multidisciplinary; Mutants; Proteins; Ring opening; Science; Science (multidisciplinary); Shells; Simulation; Trapping
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46726-6

Several actin-binding proteins (ABPs) phase separate to form condensates capable of curating the actin network shapes. Here, we use computational modeling to understand the principles of actin network organization within VASP condensate droplets. Our simulations reveal that the different actin shapes, namely shells, rings, and mixture states are highly dependent on the kinetics of VASP-actin interactions, suggesting that they arise from kinetic trapping. Specifically, we show that reducing the residence time of VASP on actin filaments reduces degree of bundling, thereby promoting assembly of shells rather than rings. We validate the model predictions experimentally using a VASP-mutant with decreased bundling capability. Finally, we investigate the ring opening within deformed droplets and found that the sphere-to-ellipsoid transition is favored under a wide range of filament lengths while the ellipsoid-to-rod transition is only permitted when filaments have a specific range of lengths. Our findings highlight key mechanisms of actin organization within phase-separated ABPs.
Here the authors perform modelling to reveal that the timescale of actin-VASP interactions plays a critical role in actin ring formation and filament length determines droplet deformation in VASP droplets: predictions from the model were tested against VASP GAB mutant.