[论文解读] Active Tension Network model of epithelial mechanics

Nicholas Noll, Madhav Mani+3 more|arXiv (Cornell University)|Aug 3, 2015

Cellular Mechanics and Interactions被引用 4

一句话总结

主动张力网络（ATN）模型提出了一种基于皮质张力主导和多边形细胞几何结构内张力依赖性皮质重塑的上皮组织力学框架。该模型预测，保角（角度保持）的细胞形变主导组织动力学，占果蝇腹侧皱褶形成过程中观察到的细胞形状变化的约90%，并可实现从组织几何结构推断局部皮质张力。

ABSTRACT

It is now widely recognized that mechanical interactions between cells play a crucial role in epithelial morphogenesis, yet understanding the mechanisms through which stress and deformation affect cell behavior remains an open problem due to the complexity inherent in the mechanical behavior of cells and the difficulty of direct measurement of forces within tissues. Theoretical can help by focusing experimental studies and by providing the framework for interpreting measurements. To that end, vertex models have introduced an approximation of epithelial cell mechanics based on a polygonal tiling representation of planar tissue. Here we formulate and analyze an Active Tension Network (ATN) model, which is based on the same polygonal representation of epithelial tissue geometry, but in addition i) assumes that mechanical balance is dominated by cortical tension and ii) introduces tension dependent local remodeling of the cortex, representing the active nature of cytoskeletal mechanics. The tension-dominance assumption has immediate implications for the geometry of cells, which we demonstrate to hold in certain types of Drosophila epithelial tissues. We demonstrate that stationary configurations of an ATN form a manifold with one degree of freedom per cell, corresponding to - i.e. angle preserving - deformations of cells, which dominate the dynamic response to perturbations. We show that isogonal modes account for approximately 90% of experimentally observed deformation of cells during the process of ventral furrow formation in Drosophila. Other interesting properties of our model include the exponential screening of mechanical stress and a negative Poisson ratio response to external uniaxial stress. We also provide a new approach to the problem of inferring local cortical tensions from the observed geometry of epithelial cells in a tissue

研究动机与目标

• 开发一个能够捕捉细胞行为主动、细胞骨架驱动特性的上皮组织力学机理模型。
• 解决从活体上皮组织的可观测几何结构推断机械力的挑战。
• 识别上皮组织在机械应力下占主导的形变模式，特别是在形态发生事件中。
• 提供一个理论框架，解释果蝇上皮形态发生中的实验观测结果，如腹侧皱褶形成。
• 证明上皮组织的机械平衡由皮质张力主导，从而可简化复杂机械相互作用。

提出的方法

• 使用平面上皮组织的多边形镶嵌表示来建模细胞几何结构。
• 假设机械平衡由皮质张力主导，将力平衡简化为基于张力的约束条件。
• 引入张力依赖的局部细胞骨架重塑，以模拟主动细胞力学行为。
• 推导静态ATN构型的几何约束，表明其构成一个每个细胞具有一个自由度的流形。
• 将模型应用于模拟单轴应力下的形变响应，揭示了指数型应力屏蔽和负泊松比行为。
• 开发一种方法，利用模型的几何和张力约束，从观测到的细胞几何结构推断局部皮质张力。

实验结果

研究问题

• RQ1 上皮组织在机械应力下占主导的形变模式是什么？它们与细胞几何结构有何关系？
• RQ2 如何从上皮细胞的观测几何结构推断局部皮质张力？
• RQ3 保角（角度保持）形变在上皮组织对机械扰动的动态响应中占主导的程度如何？
• RQ4 一个张力主导、主动重塑的上皮网络会涌现出哪些机械特性？
• RQ5 ATN模型如何解释实验观测结果，例如果蝇腹侧皱褶形成中的现象？

主要发现

• ATN模型的静态构型构成一个流形，每个细胞具有一个自由度，对应于保角（角度保持）形变。
• 保角模式占果蝇腹侧皱褶形成过程中实验观测到的细胞形状变化的约90%。
• 该模型表现出机械应力的指数型屏蔽，表明组织内部力随距离迅速衰减。
• 在单轴外部应力下，ATN模型表现出负泊松比，表明轴向压缩时横向发生膨胀。
• 该模型仅通过细胞几何结构即可推断局部皮质张力，为上皮组织中的力重建提供新方法。
• 张力主导假设准确描述了某些果蝇上皮组织的机械行为，其几何一致性已得到验证。