Actin bends over backward for directional branching

The actin cytoskeleton is the major force-generating machinery in the cell that produces pushing, pulling, and resistance forces. To perform these functions, actin filaments, with the help of many accessory proteins, form architecturally distinct structures designed for specific purposes. Thus, pushing forces are frequently generated by branched networks that assemble in the vicinity of a load and exert force using energy of actin polymerization (1, 2). Although the current level of molecular and biophysical understanding of this process is exemplary (3, 4), a key remaining question is how to maintain the directionality of the constantly branching network and prevent it from expanding into unwanted cell areas. The report by Risca et al. in PNAS (5) links the directionality of actin branching to the load-imposed curvature of actin filaments. This connection supports a direct mechanosensing role of actin filaments and explains the tunneling of actin polymerization toward the load. The molecular machinery responsible for the assembly of branched actin networks consists of a handful of proteins that were sufficient to reconstitute motility in vitro from purified components (6). A key component of the machinery is the Arp2/3 complex, a heteroheptameric protein that nucleates a new “daughter” filament as a branch on the side of a preexisting “mother” filament at a defined angle of 70°, a process called “dendritic nucleation.” After a period of elongation, growth of branches is terminated by capping proteins that bind to the growing “barbed” ends of actin filaments, and new filaments are nucleated by the Arp2/3 complex to maintain force generation (2). The dendritic nucleation machinery has many advantages for pushing force generation, explaining its broad repertoire of cellular functions that includes protrusion of lamellipodia in migrating cells, rocketing motility of membrane organelles and intracellular pathogens, formation of cell–cell junctions and …