Laboratoire de Physiologie Cellulaire Végétale, Institut de Recherches en Technologies et Sciences pour le Vivant, Centre National de la Recherche Scientifique/Commissariat à l'Energie Atomique et aux énergies alternatives/Institut National de la Recherche Agronomique/Université Joseph Fourier, 38054 Grenoble, France.
Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14440-5. doi: 10.1073/pnas.1117096109. Epub 2012 Aug 20.
Cells use their dynamic actin network to control their mechanics and motility. These networks are made of branched actin filaments generated by the Arp2/3 complex. Here we study under which conditions the microscopic organization of branched actin networks builds up a sufficient stress to trigger sustained motility. In our experimental setup, dynamic actin networks or "gels" are grown on a hard bead in a controlled minimal protein system containing actin monomers, profilin, the Arp2/3 complex and capping protein. We vary protein concentrations and follow experimentally and through simulations the shape and mechanical properties of the actin gel growing around beads. Actin gel morphology is controlled by elementary steps including "primer" contact, growth of the network, entanglement, mechanical interaction and force production. We show that varying the biochemical orchestration of these steps can lead to the loss of network cohesion and the lack of effective force production. We propose a predictive phase diagram of actin gel fate as a function of protein concentrations. This work unveils how, in growing actin networks, a tight biochemical and physical coupling smoothens initial primer-caused heterogeneities and governs force buildup and cell motility.
细胞利用其动态肌动蛋白网络来控制其力学和运动性。这些网络由由 Arp2/3 复合物产生的分支肌动蛋白丝组成。在这里，我们研究分支肌动蛋白网络的微观组织在什么条件下会产生足够的应力来触发持续的运动。在我们的实验设置中，动态肌动蛋白网络或“凝胶”在含有肌动蛋白单体、成核蛋白、Arp2/3 复合物和加帽蛋白的受控最小蛋白系统中在坚硬的珠子上生长。我们改变蛋白质浓度，并通过实验和模拟来跟踪围绕珠子生长的肌动蛋白凝胶的形状和力学特性。肌动蛋白凝胶的形态由包括“引物”接触、网络生长、缠结、力学相互作用和力产生在内的基本步骤控制。我们表明，改变这些步骤的生化协调作用会导致网络内聚性的丧失和有效力产生的缺乏。我们提出了一个作为蛋白质浓度函数的肌动蛋白凝胶命运的预测相图。这项工作揭示了在生长的肌动蛋白网络中，紧密的生化和物理偶联如何平滑初始引物引起的异质性，并控制力的建立和细胞的运动性。
