Nandi Mintu, Shekhar Shashank, Choubey Sandeep
Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, Howrah 711103, India.
Departments of Physics, Cell Biology and Biochemistry, Emory University, Atlanta, Georgia 30322, USA.
bioRxiv. 2024 Dec 12:2024.12.10.627743. doi: 10.1101/2024.12.10.627743.
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 captures the combined effects of multiple regulatory proteins on actin dynamics. We provide closed-form expressions for both time-dependent and steady-state moments of the filament length distribution. Our framework not only differentiates between various regulatory mechanisms but also serves as a powerful tool for interpreting current data and driving future experiments.
肌动蛋白丝的长度受数百种肌动蛋白结合蛋白的共同作用调控。虽然单个蛋白的作用已为人熟知,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。为解决这一问题,我们提出了一个通用动力学模型,该模型捕捉了多种调节蛋白对肌动蛋白动力学的综合影响。我们给出了丝长度分布的时间相关矩和稳态矩的封闭形式表达式。我们的框架不仅区分了各种调节机制,还作为解释当前数据和推动未来实验的有力工具。