Department of Cell Biology, Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA
Department of Cell Biology, Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Philos Trans R Soc Lond B Biol Sci. 2018 May 26;373(1747). doi: 10.1098/rstb.2017.0110.
Cell migration is driven by propulsive forces derived from polymerizing actin that pushes and extends the plasma membrane. The underlying actin network is constantly undergoing adaptation to new mechano-chemical environments and intracellular conditions. As such, mechanisms that regulate actin dynamics inherently contain multiple feedback loops and redundant pathways. Given the highly adaptable nature of such a system, studies that use only perturbation experiments (e.g. knockdowns, overexpression, pharmacological activation/inhibition, etc.) are challenged by the nonlinearity and redundancy of the pathway. In these pathway configurations, perturbation experiments at best describe the function(s) of a molecular component in an adapting (e.g. acutely drug-treated) or fully adapted (e.g. permanent gene silenced) cell system, where the targeted component now resides in a non-native equilibrium. Here, we propose how quantitative live-cell imaging and analysis of constitutive fluctuations of molecular activities can overcome these limitations. We highlight emerging actin filament barbed-end biology as a prime example of a complex, nonlinear molecular process that requires a fluctuation analytic approach, especially in an unperturbed cellular system, to decipher functional interactions of barbed-end regulators, actin polymerization and membrane protrusion.This article is part of the theme issue 'Self-organization in cell biology'.
细胞迁移是由聚合肌动蛋白产生的推进力驱动的，肌动蛋白推动并延伸了质膜。基础的肌动蛋白网络不断适应新的机械化学环境和细胞内条件。因此，调节肌动蛋白动力学的机制固有地包含多个反馈回路和冗余途径。鉴于这种系统的高度适应性，仅使用扰动实验（例如敲低、过表达、药理学激活/抑制等）的研究受到途径的非线性和冗余的挑战。在这些途径配置中，扰动实验充其量只能描述分子组件在适应（例如急性药物处理）或完全适应（例如永久性基因沉默）细胞系统中的功能，其中目标组件现在处于非天然平衡状态。在这里，我们提出了如何通过定量活细胞成像和分析分子活性的组成型波动来克服这些限制。我们强调新兴的肌动蛋白丝帽状末端生物学作为一个复杂的、非线性的分子过程的一个主要例子，该过程需要波动分析方法，特别是在未受干扰的细胞系统中，以破译帽状末端调节剂、肌动蛋白聚合和膜突的功能相互作用。本文是“细胞生物学中的自组织”专题的一部分。
