Department of Physics, Washington University in Saint Louis, One Brookings Drive, St Louis, MO 63130, USA.
Phys Biol. 2010 Jan 20;7(1):16008. doi: 10.1088/1478-3975/7/1/016008.
Transient polymerization beyond the steady state has been experimentally observed in in vitro actin polymerization time courses. These 'polymerization overshoots' have previously been described in terms of the time-dependent probabilities for binding distinct nucleotide hydrolysis states within subunits near the plus ends of actin filaments. We demonstrate a different type of overshoot dynamics where the plus-end contribution to polymerization steadily decreases relative to that of the minus end. This decrease occurs due to plus-end capping of an initial impulse of rapidly created actin filaments. We calculate the contribution of these dynamics to observed overshoot magnitudes using rate equations describing the concentration of polymerized actin. We find this contribution is highly sensitive to both initial filament concentration and plus-end capping rate. We develop an analytic formula that describes the magnitude of the overshoot as a function of these two key parameters. The overshoots we describe could be observed by current experimental methods for studying the effects of severing and branching mechanisms upon actin polymerization in the presence of plus-end capping and rapid nucleotide exchange. We also present a plausible cellular mechanism that could greatly amplify these overshoots in vivo.
在体外肌动蛋白聚合时程中，已经观察到超越稳态的瞬时聚合。这些“聚合过冲”以前是根据肌动蛋白丝正端附近亚基中结合不同核苷酸水解状态的时间依赖性概率来描述的。我们展示了一种不同类型的过冲动力学，其中聚合的正端贡献相对于负端逐渐减小。这种减少是由于快速生成的肌动蛋白丝的正端盖帽导致的。我们使用描述聚合肌动蛋白浓度的速率方程来计算这些动力学对观察到的过冲幅度的贡献。我们发现，这种贡献对初始纤维浓度和正端盖帽速率非常敏感。我们开发了一个解析公式，将过冲幅度描述为这两个关键参数的函数。在存在正端盖帽和快速核苷酸交换的情况下，通过当前用于研究切割和分支机制对肌动蛋白聚合影响的实验方法，可以观察到我们描述的过冲。我们还提出了一种可能的细胞机制，可以在体内大大放大这些过冲。
