Actin filament mechanics and branched network turnover

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SUMMARY The assembly of actin filaments into Arp2/3 complex-branched filament networks powers numerous fundamental eukaryotic cellular processes, including motility, endocytosis, and cytokinesis. Members of the actin depolymerization factor homology (ADF-H)-domain protein family, which includes cofilin and glial maturation factor (GMF), accelerate branched actin filament network reorganization and turnover. Cofilin and GMF accelerate network remodeling by debranching Arp 2/3 complex. Cofilin accelerates network turnover by fragmenting filaments and increasing the concentration of filament ends where subunits add and dissociate. This MIRA proposal integrates biochemical and biophysical approaches, including electron cryo-microscopy, microfluidics, and a recently developed microscopic magnetic cylinders assay, to develop predictive models of actin filament and filament network mechanics, remodeling and fragmentation. General principles regarding the relationship between actin filament elasticity, conformation and regulatory protein occupancy will emerge from this work.