title: Actin assembly factors regulate the gelation kinetics and architecture of F-actin networks.
abstract: Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties.
authors.affiliation: Biophysics Graduate Program, University of Chicago, Chicago, Illinois, USA.
authors.forename: Tobias T
authors.initials: TT
authors.lastname: Falzone
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Oakes
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sees
authors.forename: David R
authors.initials: DR
authors.lastname: Kovar
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Gardel
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002645:Chickens; D007700:Kinetics; D008840:Microfilament Proteins / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism; D055503:Protein Multimerization
chemical_list: D000199:Actins; D002352:Carrier Proteins; C034037:F-actin-binding proteins; D008840:Microfilament Proteins; D051304:Profilins