Turnover versus treadmilling in actin network assembly and remodeling.

Abstract

Actin networks are highly dynamic cytoskeletal structures that continuously undergo structural remodeling. One prominent way to probe these processes is via Fluorescence Recovery After Photobleaching (FRAP), which can be used to estimate the rate of turnover for filamentous actin monomers. It is thought that head-to-tail treadmilling and de novo filament nucleation constitute two primary mechanisms underlying turnover kinetics. More generally, these self-assembly activities are responsible for many important cellular functions such as force generation, cellular shape dynamics, and cellular motility. In what relative proportions filament treadmilling and de novo filament nucleation contribute to actin network turnover is still not fully understood. We used an advanced stochastic reaction-diffusion model in three dimensions, MEDYAN, to study turnover dynamics of actin networks containing Arp2/3, formin and capping protein at experimentally meaningful length- and time-scales. Our results reveal that, most commonly, treadmilling of older filaments is the main contributor to actin network turnover. On the other hand, although turnover and treadmilling are often used interchangeably, we show clear instances where this assumption would not be justified, for example, finding that rapid turnover is accompanied by slow treadmilling in highly dendritic Arp2/3 networks.