Actin kinetics shapes cortical network structure and mechanics.

Actin kinetics shapes cortical network structure and mechanics.
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DOI:
10.1126/sciadv.1501337
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发表时间:
2016-04
期刊:
影响因子:
13.6
通讯作者:
Kruse K
Kruse K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Fritzsche M;Erlenkämper C;Moeendarbary E;Charras G;Kruse K

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细胞通过调节肌动蛋白前体的浓度和肌动蛋白核因子的活性来调整它们的宏观机械性能。动物细胞的肌动蛋白皮质是细胞力学的主要决定因素。皮质肌动蛋白细丝的持续周转使细胞能够对刺激做出快速反应。最近的研究表明,大多数皮质肌动蛋白只由两个肌动蛋白核因子产生,即Arp2/3复合体和Forin DIAPH1。然而,我们对它们的相互作用、它们的动力学以及它们在活细胞内成核的细丝的长度分布的了解很差。这些知识对于从基本的聚合物物理原理中彻底理解细胞过程和细胞力学是必要的。我们通过使用单分子荧光成像和随机模拟相结合的方法来确定活细胞中的皮质集合率。我们发现,平均而言,甲醛成核丝的长度是Arp2/3成核丝的10倍。尽管福尔明生成的细丝只占肌动蛋白细丝的不到10%,但机械测量表明它们是皮质弹性的重要决定因素。因此,调节肌动蛋白核因子的活性以改变细丝长度分布可能是一种允许细胞根据其生理需要调整其宏观机械性能的机制。
Cells adjust their macroscopic mechanical properties by tuning the actin protomer concentration and activity of actin nucleators. The actin cortex of animal cells is the main determinant of cellular mechanics. The continuous turnover of cortical actin filaments enables cells to quickly respond to stimuli. Recent work has shown that most of the cortical actin is generated by only two actin nucleators, the Arp2/3 complex and the formin Diaph1. However, our understanding of their interplay, their kinetics, and the length distribution of the filaments that they nucleate within living cells is poor. Such knowledge is necessary for a thorough comprehension of cellular processes and cell mechanics from basic polymer physics principles. We determined cortical assembly rates in living cells by using single-molecule fluorescence imaging in combination with stochastic simulations. We find that formin-nucleated filaments are, on average, 10 times longer than Arp2/3-nucleated filaments. Although formin-generated filaments represent less than 10% of all actin filaments, mechanical measurements indicate that they are important determinants of cortical elasticity. Tuning the activity of actin nucleators to alter filament length distribution may thus be a mechanism allowing cells to adjust their macroscopic mechanical properties to their physiological needs.