Adhesion dynamics regulate cell intercalation behaviour in an active tissue
Adhesion dynamics regulate cell intercalation behaviour in an active tissue
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粘附动力学调节活性组织中的细胞嵌入行为
DOI：
10.1101/2021.04.11.439313
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Nestor-Bergmann A
中科院分区：
文献类型：
--
作者：
Nestor-Bergmann A
细胞嵌入是形态发生和伤口愈合的关键细胞行为，其中局部细胞邻居交换可引起剧烈的组织变形，如体轴延伸。在这里，我们开发了一个机械模型来理解上皮组织背景下活跃的细胞插层行为。扩展现有的描述，如顶点模型，每个细胞的连接肌动球蛋白皮层被建模为连续的形态弹性棒，明确地表示在双细胞连接处彼此面对的皮层。细胞被直接描述为驱动动力学的关键亚细胞成分，包括来自收缩的肌动球蛋白皮层和偶联的粘附分子的局部应力。这种多尺度的对抗皮层公式揭示了驱动组织动力学的关键行为，如细胞-细胞剪切和连接物质流过细胞顶点。我们表明，细胞邻居交换可以由纯粹的连接机制驱动。单个双细胞结的主动收缩性和粘性周转足以收缩和移除一个结。接下来，4路顶点被分解，一个新的正交结被动扩展。粘附时间尺度定义了摩擦粘度，这是这些动力学的重要调节器，调节组织中的张力传递以及结收缩和生长的速度。该模型还预测，当一个顶点为许多细胞所共有时形成的玫瑰花结，很可能发生在具有高黏着摩擦的活性组织中。细胞嵌入，或邻居交换，是一种关键的行为，可以驱动组织变形，消散压力，促进伤口愈合。大量的实验工作已经确定了促进嵌入的关键分子，但对它们的物理作用仍然缺乏共识和理解。现有的生物物理模型表示细胞与细胞之间的单边接触，不能研究涉及耦合细胞皮层之间剪切的插层的连续动力学。通过对细胞皮质的连续描述，明确地将相邻皮质与粘附耦合，我们定义了成功的相邻交换所需的生物物理条件。此外，我们展示了粘附分子的周转如何指定调节活跃组织动力学的粘性摩擦。
Cell intercalation is a key cell behaviour of morphogenesis and wound healing, where local cell neighbour exchanges can cause dramatic tissue deformations such as body axis extension. Here, we develop a mechanical model to understand active cell intercalation behaviours in the context of an epithelial tissue. Extending existing descriptions, such as vertex models, the junctional actomyosin cortex of every cell is modelled as a continuum morphoelastic rod, explicitly representing cortices facing each other at bicellular junctions. Cells are described directly in terms of the key subcellular constituents that drive dynamics, with localised stresses from the contractile actomyosin cortex and adhesion molecules coupling apposed cortices. This multi-scale apposed-cortex formulation reveals key behaviours that drive tissue dynamics, such as cell-cell shearing and flow of junctional material past cell vertices. We show that cell neighbour exchanges can be driven by purely junctional mechanisms. Active contractility and viscous turnover in a single bicellular junction are sufficient to shrink and remove a junction. Next, the 4-way vertex is resolved and a new, orthogonal junction extends passively. The adhesion timescale defines a frictional viscosity that is an important regulator of these dynamics, modulating tension transmission in the tissue as well as the speeds of junction shrinkage and growth. The model additionally predicts that rosettes, which form when a vertex becomes common to many cells, are likely to occur in active tissues with high adhesive friction.SIGNIFICANCECell intercalation, or neighbour exchange, is a crucial behaviour that can drive tissue deformations, dissipate stress and facilitate wound healing. Substantial experimental work has identified the key molecular players facilitating intercalation, but there remains a lack of consensus and understanding of their physical roles. Existing biophysical models that represent cell-cell contacts with single edges cannot study the continuous dynamics of intercalation, involving shear between coupled cell cortices. Deriving a continuum description of the cell cortex, explicitly coupling neighbouring cortices with adhesions, we define the biophysical conditions required for successful neighbour exchanges. Furthermore, we show how the turnover of adhesion molecules specifies a viscous friction that regulates active tissue dynamics.
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DOI：
--
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