Department of Chemical Engineering, Columbia University, New York, New York.
Cytoskeleton (Hoboken). 2019 Nov;76(11-12):611-625. doi: 10.1002/cm.21558. Epub 2019 Sep 11.
A fundamental challenge in cell biology is to understand how cells generate actomyosin-based contractile force. Here we study the actomyosin contractile ring that divides cells during cytokinesis and generates tension by a mechanism that remains poorly understood. Long ago a muscle-like sliding filament mechanism was proposed, but evidence for sarcomeric organization in contractile rings is lacking. We develop a coarse-grained model of the fission yeast cytokinetic ring, incorporating the two myosin-II isoforms Myo2 and Myp2 and severely constrained by experimental data. The model predicts that ring tension is indeed generated by a sliding filament mechanism, but a spatially and temporally homogeneous version of that in muscle. In this mechanism all pairs of oppositely oriented actin filaments are rendered tense as they are pulled toward one another and slide through clusters of myosin-II. The mechanism relies on anchoring of actin filament barbed ends to the plasma membrane, which resists lateral motion and enables filaments to become tense when pulled by myosin-II. A second fixed filament component is independent of lateral anchoring, generated by chains of like-oriented actin filaments. Myo2 contributes to both components, while Myp2 contributes to the sliding filament component only. In the face of instabilities inherent to actomyosin contractility, organizational homeostasis is maintained by rapid turnover of Myo2 and Myp2, and by drag forces that resist lateral motion of actin, Myo2 and Myp2. Thus, sliding and fixed filament mechanisms contribute to tension in the disordered contractile ring without the need for the sarcomeric architecture of muscle.
细胞生物学的一个基本挑战是理解细胞如何产生肌动球蛋白依赖性收缩力。在这里，我们研究了有丝分裂细胞分裂过程中的肌动球蛋白收缩环，该收缩环通过一种机制产生张力，而这种机制仍知之甚少。很久以前就提出了类似于肌肉的滑动丝机制，但在收缩环中缺乏肌节组织的证据。我们开发了一个裂殖酵母胞质分裂环的粗粒化模型，该模型包含两种肌球蛋白-II 同工型 Myo2 和 Myp2，并受到实验数据的严格限制。该模型预测，环张力确实是通过滑动丝机制产生的，但与肌肉中的机制在空间和时间上是均匀的。在这种机制中，当相互靠近的相反取向的肌动蛋白丝对被拉动并通过肌球蛋白-II 簇滑动时，所有对肌动蛋白丝都会变得紧张。该机制依赖于肌动蛋白丝的棘突与质膜的锚定，这抵抗了侧向运动，使肌动蛋白丝在被肌球蛋白-II 拉动时变得紧张。第二个固定丝组件与侧向锚定无关，由同向肌动蛋白丝链产生。Myo2 对两个组件都有贡献，而 Myp2 仅对滑动丝组件有贡献。面对肌动球蛋白收缩固有不稳定性，Myo2 和 Myp2 的快速周转以及阻力拖曳力维持了组织内稳态，这些力抵抗肌动蛋白、Myo2 和 Myp2 的侧向运动。因此，滑动和固定丝机制在无序收缩环中产生张力，而无需肌肉的肌节结构。
