Remarkable structural transformations of actin bundles are driven by their initial polarity, motor activity, crosslinking, and filament treadmilling
Remarkable structural transformations of actin bundles are driven by their initial polarity, motor activity, crosslinking, and filament treadmilling
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DOI：
10.1371/journal.pcbi.1007156
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发表时间：
2019-07-01
影响因子：
4.3
通讯作者：
Papoian, Garegin A.
中科院分区：
文献类型：
--
作者：
Chandrasekaran, Aravind;Upadhyaya, Arpita;Papoian, Garegin A.
成束的肌动蛋白结构在维持细胞形状、帮助力传递到细胞外基质和从细胞外基质传递力以及影响细胞运动性方面起关键作用。最近的研究也揭示了新的细节应力产生，力的传递和肌动蛋白束的收缩性。在这项工作中，我们主要感兴趣的问题是什么决定了肌动蛋白束的稳定性和什么样的网络几何不稳定束最终过渡。为了解决这个问题，我们使用了MEDYAN机械化学力场，在3D中模拟了几个微米长的肌动蛋白束，同时考虑了一套全面的化学，机械和运输过程。在我们的研究中，我们开发了一个层次聚类算法的分类不同的长时间尺度形态。我们的主要发现是，最初单极束显着更稳定的非极性初始配置相比。由于肌球蛋白的活性，后者束内的细丝容易相对于彼此滑动，产生松散的网络，随后可能严重扭曲。在高肌球蛋白浓度下，观察到一个形态过渡到紫菀样的几何形状。我们还研究了肌动蛋白的纤维束铣削率如何影响束动力学，并发现，增强纤维束铣削导致网络的碎片化和解体，而这个过程是反对肌球蛋白和交联活动。有趣的是，具有初始非极性几何形状的螺旋铣削束最终发展为基于细丝末端的相对位置的整个网络形态，例如肌节状组织。我们发现，非极性束显示出显着的敏感性，环境条件下，这可能是重要的，使快速的细胞骨架结构重组和适应细胞内和细胞外的线索。
Bundled actin structures play a key role in maintaining cellular shape, in aiding force transmission to and from extracellular substrates, and in affecting cellular motility. Recent studies have also brought to light new details on stress generation, force transmission and contractility of actin bundles. In this work, we are primarily interested in the question of what determines the stability of actin bundles and what network geometries do unstable bundles eventually transition to. To address this problem, we used the MEDYAN mechano-chemical force field, modeling several micron-long actin bundles in 3D, while accounting for a comprehensive set of chemical, mechanical and transport processes. We developed a hierarchical clustering algorithm for classification of the different long time scale morphologies in our study. Our main finding is that initially unipolar bundles are significantly more stable compared with an apolar initial configuration. Filaments within the latter bundles slide easily with respect to each other due to myosin activity, producing a loose network that can be subsequently severely distorted. At high myosin concentrations, a morphological transition to aster-like geometries was observed. We also investigated how actin treadmilling rates influence bundle dynamics, and found that enhanced treadmilling leads to network fragmentation and disintegration, while this process is opposed by myosin and crosslinking activities. Interestingly, treadmilling bundles with an initial apolar geometry eventually evolve to a whole gamut of network morphologies based on relative positions of filament ends, such as sarcomere-like organization. We found that apolar bundles show a remarkable sensitivity to environmental conditions, which may be important in enabling rapid cytoskeletal structural reorganization and adaptation in response to intracellular and extracellular cues.