Grenoble-Alpes University, CNRS, LIPHy, 38000, Grenoble, France.
Phys Rev E. 2020 Jan;101(1-1):012420. doi: 10.1103/PhysRevE.101.012420.
Integrin receptor (IR) clustering is an example of pattern self-organization in biological systems. This paper describes a model for receptor activation whose content is guided by two major principles in cellular signal transduction: (i) Proteins cycle between different conformational states; (ii) the dynamics of their conformational dynamics is environment dependent. Based on a simple activation pathway where these two hypotheses are formulated in a self-consistent way, this paper focuses mainly on stochastic simulations valid in the limit of a small number of molecules. It is shown that coherent clustering can lead to digital signaling and receptor competition in biochemical systems where the model gives a recruitment mechanism for the reinforcement of the mechanical linkage with the extracellular matrix. Together with previous works, this paper provides a workable model for cell integrin adhesive structures when feedback mediated by membrane diffusing signals is dominant. Consequences are discussed in the framework of published data concerning the local production of a key phospholipid for cell signaling (PIP_{2}).
整合素受体 (IR) 聚类是生物系统中模式自组织的一个例子。本文描述了一个受体激活模型，其内容受细胞信号转导中的两个主要原则指导：(i) 蛋白质在不同构象状态之间循环；(ii) 构象动力学的动态变化依赖于环境。基于一个简单的激活途径，其中这两个假设以自洽的方式表述，本文主要关注在少量分子的极限情况下有效的随机模拟。结果表明，在模型为细胞外基质的机械连接提供增强的招募机制的生化系统中，相干聚类可导致数字信号和受体竞争。本文与之前的工作一起，为反馈介导的膜扩散信号占主导地位时的细胞整合素黏附结构提供了一个可行的模型。在关于细胞信号关键磷脂 (PIP_2) 的局部产生的已发表数据的框架内讨论了结果。
