Regulation of F-actin size heterogeneity by formin and capping proteins

Actin filaments are one of the main components of the eukaryotic cytoskeleton that regulate cellular architecture and mechanical properties. While previous studies have mostly focused on the length control of individual actin filaments, it remains poorly understood how actin filaments in a cell regulate heterogeneity in size using a limited set of monomeric building blocks and actin binding proteins (ABP). Here we develop a theoretical model for the regulation of actin filament size heterogeneity by nucleation and growth rate modulation in a limiting pool of monomers and ABPs. We then investigate the roles of filament growth inhibition and promotion by capping and formin proteins on filament size heterogeneity. We find that heterogeneity can be increased by strong growth inhibition by capping and weak growth promotion by formin. A combination of both can give rise to bimodal size distribution and highly heterogeneous size distribution. Our study quantitatively predicts how heterogeneity in actin filament size can be regulated by tuning nucleation and growth rates. This emerging heterogeneity effects network morphology and distinct filament subpopulations may be crucial for building specialized actin structures (e.g., stress fiber) in a cell.