Adhesion-regulated junction slippage controls cell intercalation dynamics in an Apposed-Cortex Adhesion Model.
Adhesion-regulated junction slippage controls cell intercalation dynamics in an Apposed-Cortex Adhesion Model.
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DOI：
10.1371/journal.pcbi.1009812
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发表时间：
2022-01
影响因子：
4.3
通讯作者：
Sanson B
中科院分区：
文献类型：
--
作者：
Nestor-Bergmann A;Blanchard GB;Hervieux N;Fletcher AG;Étienne J;Sanson B
细胞嵌入是形态发生和伤口愈合的关键细胞行为，其中局部细胞相邻交换可引起剧烈的组织变形，例如体轴延伸。大量的实验工作已经确定了促进插层的关键分子，但仍然缺乏共识和理解他们的物理作用。现有的生物物理模型，代表细胞与细胞接触的单边缘不能研究细胞邻居交换作为一个连续的过程，相邻的细胞皮层必须解偶联。在这里，我们开发了一个贴壁皮层粘附模型（ACAM），以了解在二维上皮组织的背景下，活跃的细胞嵌入行为。每个细胞的交界处肌动球蛋白皮质被建模为一个连续的粘弹性绳环，明确表示皮质面对彼此在双细胞交界处和粘附分子耦合。模型参数与驱动动力学的关键亚细胞参与者的属性直接相关，从而提供了对细胞行为的多尺度理解。我们表明，积极的细胞邻居交换可以驱动纯交界机制。单个双细胞连接处的主动收缩性和皮质周转足以收缩和去除连接处。接下来，一个新的正交结被动延伸。ACAM揭示了粘附分子的周转如何通过控制并列细胞皮质之间的滑动来调节张力传递和连接变形率。该模型还预测，当一个顶点对许多细胞变得共同时，形成的突起更有可能发生在具有粘附分子强摩擦力的活跃嵌入组织中。在发育过程中，组织经历了巨大的形状变化，以建立和重塑器官。在许多情况下，这些组织水平的变形是由组成细胞的主动重组驱动的。这种嵌入过程涉及多个单元相邻交换，其中两个单元之间共享的界面被移除并且新的界面生长。参与邻居交换的关键分子，如收缩马达蛋白和粘附复合物，现在是众所周知的。然而，它们的物理特性如何促进这一过程仍然知之甚少。例如，细胞如何保持足够的粘附接触，同时主动地彼此解偶联？那么，一个新的界面如何在收缩的环境中生长呢？许多现有的生物物理模型不能回答这样的问题，由于代表共享的细胞界面作为离散的元素，不能解耦。在本文中，我们开发了一个模型，代表细胞皮质的收缩绳环耦合的粘连。我们概述了成功的邻居交换所需的条件，在已知的分子驱动的过程中的属性。该模型预测，组织动力学强烈依赖于相邻皮质相对于彼此滑动的能力，这是由粘附周转调节。
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. 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 cell neighbour exchange as a continuous process, where neighbouring cell cortices must uncouple. Here, we develop an Apposed-Cortex Adhesion Model (ACAM) to understand active cell intercalation behaviours in the context of a 2D epithelial tissue. The junctional actomyosin cortex of every cell is modelled as a continuous viscoelastic rope-loop, explicitly representing cortices facing each other at bicellular junctions and the adhesion molecules that couple them. The model parameters relate directly to the properties of the key subcellular players that drive dynamics, providing a multi-scale understanding of cell behaviours. We show that active cell neighbour exchanges can be driven by purely junctional mechanisms. Active contractility and cortical turnover in a single bicellular junction are sufficient to shrink and remove a junction. Next, a new, orthogonal junction extends passively. The ACAM reveals how the turnover of adhesion molecules regulates tension transmission and junction deformation rates by controlling slippage between apposed cell cortices. The model additionally predicts that rosettes, which form when a vertex becomes common to many cells, are more likely to occur in actively intercalating tissues with strong friction from adhesion molecules. During development tissues undergo dramatic shape changes to build and reshape organs. In many instances, these tissue-level deformations are driven by the active reorganisation of the constituent cells. This intercalation process involves multiple cell neighbour exchanges, where an interface shared between two cells is removed and a new interface is grown. The key molecular players involved in neighbour exchanges, such as contractile motors proteins and adhesion complexes, are now well-known. However, how their physical properties facilitate the process remains poorly understood. For example, how do cells maintain sufficient adhesive contact while actively uncoupling from one another? Then, how does a new interface grow in a contractile environment? Many existing biophysical models cannot answer such questions, due to representing shared cell interfaces as discrete elements that cannot uncouple. In this paper, we develop a model that represents cell cortices as contractile rope-loops coupled by adhesions. We outline the conditions required for successful neighbour exchanges, in terms of the properties of the known molecules that drive the process. The model predicts that tissue dynamics depend strongly on the ability of neighbouring cortices to slip relative to one another, which is regulated by adhesion turnover.
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影响因子：
64.8
作者：
Cavey, Matthieu;Rauzi, Matteo;Lecuit, Thomas
通讯作者：
Lecuit, Thomas
影响因子：
11.8
作者：
Acharya, Bipul R.;Nestor-Bergmann, Alexander;Yap, Alpha S.
通讯作者：
Yap, Alpha S.
影响因子：
9.8
作者：
Finegan, Tara M.;Hervieux, Nathan;Sanson, Benedicte
通讯作者：
Sanson, Benedicte
DOI：
10.1126/science.1254211
发表时间：
2014-10-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Buckley CD;Tan J;Anderson KL;Hanein D;Volkmann N;Weis WI;Nelson WJ;Dunn AR
通讯作者：
Dunn AR
影响因子：
21.3
作者：
Collinet, Claudio;Rauzi, Matteo;Lecuit, Thomas
通讯作者：
Lecuit, Thomas