Flat clathrin lattices are linked to metastatic potential in colorectal cancer

Cresens, Charlotte; Solís‐Fernández, Guillermo; Tiwari, Astha; Nuyts, Rik; Hofkens, Johan; Barderas, Rodrigo; Rocha, Susana

doi:10.1101/2023.01.12.520576

Cited by 1 publication

(1 citation statement)

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“…For example, in cell spreading, actin forms a dendritic branched architecture at the lamellipodium (42) but forms bundled force-generating structures in filopodia (43) and in stress fibers (44,45). Different actin architectures are also seen in endocytosis (41,(46)(47)(48). Each of these network architectures results from a combination of filament-level modifications of various actin binding proteins (49), along with their respective time scales of interaction, which are determined by the kinetics of binding and unbinding (50)(51)(52)(53)(54).…”

Section: Introductionmentioning

confidence: 99%

Kinetic trapping organizes actin filaments within liquid-like protein droplets

Chandrasekaran

Graham

Stachowiak

et al. 2023

Preprint

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Actin is essential for various cellular functions such as growth, migration, and endocytosis. Recent evidence suggests that several actin-binding proteins phase separate to form condensates and that actin networks have different architectures in these droplets. In this study, we use computational modeling to investigate the conditions under which actin forms different network organizations in VASP droplets. Our simulations reveal that the binding and unbinding rates of actin and VASP determine the probability of formation of shells and rings, with shells being more probable than rings. The different actin networks are highly dependent on the kinetics of VASP-actin interactions, suggesting that they arise from kinetic trapping. Specifically, we showed that reducing the residence time of VASP on actin filaments promotes assembly of shells rather than rings, where rings require a greater degree of actin bundling. These predictions were tested experimentally using a mutant of VASP, which has decreased bundling capability. Experiments reveal an increase in the abundance of shells in VASP droplets, consistent with our predictions. Finally, we investigated the arrangements of filaments within deformed droplets and found that the filament length largely determines whether a droplet will straighten into a bundle or remain kinetically trapped in a ring-like architecture. The sphere-to-ellipsoid transition is favored under a wide range of conditions while the ellipse-to-rod transition is only permitted when filaments have a specific range of lengths. Our findings have implications for understanding how the interactions between phase-separated actin binding proteins and actin filaments can give rise to different actin network architectures.

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