Nandi Mintu, Shekhar Shashank, Choubey Sandeep
Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, Howrah, India.
Departments of Physics, Cell Biology and Biochemistry, Emory University, Atlanta, Georgia, United States of America.
PLoS Comput Biol. 2025 Sep 8;21(9):e1013434. doi: 10.1371/journal.pcbi.1013434. eCollection 2025 Sep.
The length of actin filaments is regulated by the combined action of hundreds of actin-binding proteins. While the roles of individual proteins are well understood, how they combine to regulate actin dynamics in vivo remains unclear. Recent advances in microscopy have enabled precise, high-throughput measurements of filament lengths over time. However, the absence of a unified theoretical framework has hindered a mechanistic understanding of the multicomponent regulation of actin dynamics. To address this, we propose a general kinetic model that incorporates the combined effects of an arbitrary number of regulatory proteins on actin dynamics. We derive exact closed-form expressions for the moments of (1) the distribution of filament lengths over time and (2) the long-time distribution of changes in filament lengths within a fixed time window. We show that these moments allow us to distinguish between different regulatory mechanisms of multicomponent regulation of actin dynamics. Our theoretical framework provides a powerful tool for interpreting existing data and guiding future experiments.
肌动蛋白丝的长度受数百种肌动蛋白结合蛋白的联合作用调控。虽然单个蛋白质的作用已得到充分了解，但它们如何在体内共同调节肌动蛋白动力学仍不清楚。显微镜技术的最新进展使得能够随时间精确、高通量地测量丝的长度。然而，缺乏统一的理论框架阻碍了对肌动蛋白动力学多组分调节的机制理解。为了解决这个问题，我们提出了一个通用动力学模型，该模型纳入了任意数量的调节蛋白对肌动蛋白动力学的联合作用。我们推导出了关于（1）丝长度随时间分布的矩以及（2）在固定时间窗口内丝长度变化的长期分布的精确封闭形式表达式。我们表明，这些矩使我们能够区分肌动蛋白动力学多组分调节的不同调节机制。我们的理论框架为解释现有数据和指导未来实验提供了一个强大的工具。
