Emergence and maintenance of variable-length actin filaments in a limiting pool of building blocks
Emergence and maintenance of variable-length actin filaments in a limiting pool of building blocks
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DOI：
10.1016/j.bpj.2022.05.014
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发表时间：
2022-06-21
影响因子：
3.4
通讯作者：
Banerjee, Shiladitya
中科院分区：
文献类型：
--
作者：
Banerjee, Deb Sankar;Banerjee, Shiladitya
肌动蛋白是真核细胞骨架的关键结构成分之一，调节细胞结构和力学性能。肌动蛋白丝的长度和组织的动态调节对细胞粘附、运动和分裂等许多生理过程的控制至关重要。虽然以前的研究主要集中在控制单个肌动蛋白丝长度的机制上，但人们对细胞中不同的肌动蛋白丝群体如何使用同一组分子构建块保持不同的长度仍然知之甚少。在这里，我们建立了一个理论模型，通过在有限的单体池中肌动蛋白结合蛋白的成核和生长速率调节来调节多个肌动蛋白丝的长度。我们首先表明肌动蛋白丝的自发成核自然导致丝长度分布的异质性。然后，我们研究了封顶蛋白抑制纤维生长和双胍蛋白促进生长对纤维长度分布的影响。我们发现生长抑制可以增加纤维长度的异质性，而生长促进剂对长度的异质性影响不显著。有趣的是，长丝生长抑制剂和生长促进剂之间的竞争可以导致长丝长度分布的双峰，以及具有较大统计色散的高度非均匀的长度分布。我们定量预测如何通过调整丝状肌动蛋白成核和生长速率来调节肌动蛋白丝长度的异质性，从而产生不同长度的不同丝亚群。
Actin 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 length of single actin filaments, it remains poorly understood how distinct actin filament populations in cells maintain different lengths 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 heterogeneity. 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 filamentous actin nucleation and growth rates in order to create distinct filament subpopulations with different lengths.