Turnover versus Treadmilling in Actin Network Assembly and Remodeling

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 \textit{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 timescales. 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.

肌动蛋白网络是一种高度动态的细胞骨架结构，其结构持续进行重塑。探查这些过程的一种显著方法是通过荧光恢复后漂白（FRAP）技术，该技术可用于估算细丝状肌动蛋白单体周转速率。据认为，头部至尾部 treadmilling 和从头开始形成细丝是周转动力学背后的两种主要机制。更普遍地，这些自组装活动负责许多重要的细胞功能，如力生成、细胞形状动力学和细胞运动。然而，关于细丝 treadmilling 和从头开始形成细丝在肌动蛋白网络周转中的相对贡献比例，尚未完全明了。我们采用了一种先进的具有三维空间特性的随机反应扩散模型——MEDYAN，在实验上具有意义的长度和时间尺度上研究了包含 Arp2/3、formin 和封顶蛋白的肌动蛋白网络的周转动力学。我们的研究结果揭示，最常见的情况是，较老细丝的 treadmilling 是肌动蛋白网络周转的主要贡献者。另一方面，尽管周转和 treadmilling 常被互换使用，但我们展示了这一假设并不总是合理的实例，例如，发现在高度树突状的 Arp2/3 网络中，快速周转伴随着缓慢的 treadmilling。