Actin filament mechanics and branched network turnover

SUMMARY The assembly of actin filaments into Arp2/3 complex-branched filament networks powers numerous fundamental eukaryotic cellular processes, including motility, endocytosis, and cytokinesis. Reorganization and disassembly of these branched networks recycle actin and regulatory protein components, permitting continual force production and sustained motility. This MIRA proposal integrates biochemical and biophysical experiments and theory to develop predictive models of actin filament and network mechanics, assembly, remodeling, and recycling. Completing the proposed research will fill missing gaps in knowledge of the Arp2/3 complex debranching mechanism, specifically how it is regulated by bound nucleotide and force, how regulatory proteins modulate Arp2/3 complex activity, and the significance of actin isoforms. The proposed research will also determine how the kinetic properties of an RNA helicase motor protein essential for nuclear mRNA export and a purinergic signaling enzyme involved in calcification have adapted to fulfill their physiological roles.