Center for Computational Biology, Flatiron Institute, New York, New York.
Departments of Mechanical Engineering, and Mathematics, Michigan Institute for Computational Discovery & Engineering, University of Michigan, Ann Arbor, Michigan.
Biophys J. 2022 Aug 16;121(16):3162-3171. doi: 10.1016/j.bpj.2022.06.033. Epub 2022 Jul 1.
Numerous engineered and natural systems form through reinforcement and stabilization of a deformed configuration that was generated by a transient force. An important class of such structures arises during gametogenesis, when a dividing cell undergoes incomplete cytokinesis, giving rise to daughter cells that remain connected through a stabilized intercellular bridge (ICB). ICBs can form through arrest of the contractile cytokinetic furrow and its subsequent stabilization. Despite knowledge of the molecular components, the mechanics underlying robust ICB assembly and the interplay between ring contractility and stiffening are poorly understood. Here, we report joint experimental and theoretical work that explores the physics underlying robust ICB assembly. We develop a continuum mechanics model that reveals the minimal requirements for the formation of stable ICBs, and validate the model's equilibrium predictions through a tabletop experimental analog. With insight into the equilibrium states, we turn to the dynamics: we demonstrate that contractility and stiffening are in dynamic competition and that the time intervals of their action must overlap to ensure assembly of ICBs of biologically observed proportions. Our results highlight a mechanism in which deformation and remodeling are tightly coordinated-one that is applicable to several mechanics-based applications and is a common theme in biological systems spanning several length scales.
许多工程和自然系统都是通过对瞬态力产生的变形构型进行强化和稳定而形成的。在配子发生过程中会产生一类重要的此类结构，此时一个正在分裂的细胞经历不完全胞质分裂，导致子细胞通过稳定的细胞间桥（ICB）连接在一起。ICB 可以通过收缩性胞质分裂沟的阻滞及其随后的稳定化而形成。尽管已经了解了分子成分，但对坚固的 ICB 组装的力学基础以及环收缩性和变硬之间的相互作用仍知之甚少。在这里，我们报告了一项联合实验和理论工作，探讨了坚固的 ICB 组装的物理基础。我们开发了一个连续体力学模型，揭示了形成稳定 ICB 的最小要求，并通过桌面实验模拟验证了模型的平衡预测。深入了解平衡状态后，我们转向动力学：我们证明了收缩性和变硬处于动态竞争中，它们的作用时间间隔必须重叠，以确保组装出具有生物学观察到的比例的 ICB。我们的结果突出了一种变形和重塑紧密协调的机制——该机制适用于几种基于力学的应用，并且是跨越多个长度尺度的几个生物系统的共同主题。
