Emergence and maintenance of different sized actin filaments in a common pool of building blocks

Abstract

ABSTRACTActin is one of the key structural components of the eukaryotic cytoskeleton that regulates cellular architecture and mechanical properties. Dynamic regulation of actin filament length and organization is essential for the control of many physiological processes including cell adhesion, motility and division. While previous studies have mostly focused on the mechanisms controlling the mean length of individual actin filaments, it remains poorly understood how distinct actin filament populations in cells maintain different size using the same set of molecular building blocks. Here we develop a theoretical model for the length regulation of multiple actin filaments by nucleation and growth rate modulation by actin binding proteins in a limiting pool of monomers. We first show that spontaneous nucleation of actin filaments naturally leads to heterogeneities in filament length distribution. We then investigate the effects of filament growth inhibition by capping proteins and growth promotion by formin proteins on filament length distribution. We find that filament length heterogeneity can be increased by growth inhibition, whereas growth promoters do not significantly affect length heterogeneities. Interestingly, a competition between filament growth inhibitors and growth promoters can give rise to bimodal filament length distribution as well as a highly heterogeneous length distribution with large statistical dispersion. We quantitatively predict how heterogeneity in actin filament length can be modulated by tuning F-actin nucleation and growth rates in order to create distinct filament subpopulations with different lengths.SIGNIFICANCEActin filaments organize into different functional network architectures within eukaryotic cells. To maintain different actin network architectures, actin filaments of different lengths are often required. How cells regulate the length heterogeneity in actin filaments is not well understood. Here we show that the modulation of filament growth rates and nucleation rate by binding partners like formin and capping proteins can regulate the emergent length heterogeneity in the filament population and can create distinct sub-populations with different lengths. Our study sheds light into how actin binding proteins can control various aspects of filament size distribution by tuning their concentration or expression levels in the cell.