In Silico Reconstitution of Actin-Based Symmetry Breaking and Motility
In Silico Reconstitution of Actin-Based Symmetry Breaking and Motility
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DOI：
10.1371/journal.pbio.1000201
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发表时间：
2009-09-01
期刊：
影响因子：
9.8
通讯作者：
Mullins, R. Dyche
中科院分区：
文献类型：
--
作者：
Dayel, Mark J.;Akin, Orkun;Mullins, R. Dyche
真核细胞组装交联肌动蛋白丝的粘弹性网络以控制其形状、机械性质和运动性。一类重要的肌动蛋白网络由Arp 2/3复合物成核，并驱动运动细胞前缘的膜突起和病原体如单核细胞增生李斯特菌的细胞内运动。这些网络可以从纯化的组分在体外重构，以驱动球形微米尺寸的珠粒的运动性。弹性凝胶模型已经成功地解释了这些网络如何打破对称性，但它们如何产生定向运动力却不太清楚。我们结合了数值模拟与体外实验，使用建立在弹性凝胶模型基础上的累积粒子弹簧（APS）模型，在计算机上重建这些能动肌动蛋白网络的行为，并展示了对称性破缺和持续运动的简单直观机制。APS模型解释了所观察到的平滑和脉动运动之间的过渡，以及由几何形状和条件差异引起的网络结构的细微变化。我们的研究结果还解释了侧面对称性破缺和运动的细长珠，并表明，弹性反冲，虽然重要的对称性破缺和脉动运动，是没有必要的顺利定向运动。APS模型演示了少量的粘弹性网络参数和构造规则如何足以重新捕获运动肌动蛋白网络的复杂行为。事实上，该模型不仅反映了我们在体外的观察，而且还作出了新的预测，我们通过实验证实，表明该模型捕捉到了这个系统中肌动蛋白为基础的运动的本质。
Eukaryotic cells assemble viscoelastic networks of crosslinked actin filaments to control their shape, mechanical properties, and motility. One important class of actin network is nucleated by the Arp2/3 complex and drives both membrane protrusion at the leading edge of motile cells and intracellular motility of pathogens such as Listeria monocytogenes. These networks can be reconstituted in vitro from purified components to drive the motility of spherical micron-sized beads. An Elastic Gel model has been successful in explaining how these networks break symmetry, but how they produce directed motile force has been less clear. We have combined numerical simulations with in vitro experiments to reconstitute the behavior of these motile actin networks in silico using an Accumulative Particle-Spring (APS) model that builds on the Elastic Gel model, and demonstrates simple intuitive mechanisms for both symmetry breaking and sustained motility. The APS model explains observed transitions between smooth and pulsatile motion as well as subtle variations in network architecture caused by differences in geometry and conditions. Our findings also explain sideways symmetry breaking and motility of elongated beads, and show that elastic recoil, though important for symmetry breaking and pulsatile motion, is not necessary for smooth directional motility. The APS model demonstrates how a small number of viscoelastic network parameters and construction rules suffice to recapture the complex behavior of motile actin networks. The fact that the model not only mirrors our in vitro observations, but also makes novel predictions that we confirm by experiment, suggests that the model captures much of the essence of actin-based motility in this system.