Chassonnery Pauline, Paupert Jenny, Lorsignol Anne, Séverac Childérick, Ousset Marielle, Degond Pierre, Casteilla Louis, Peurichard Diane
RESTORE, Université de Toulouse, Inserm U1031, EFS, INP-ENVT, UPS, CNRS ERL5311, Toulouse, France.
Inria Paris, team MAMBA, Sorbonne Université, CNRS, Université de Paris, Laboratoire Jacques-Louis Lions UMR7598, 75005 Paris, France.
R Soc Open Sci. 2024 Jan 31;11(1):231456. doi: 10.1098/rsos.231456. eCollection 2024 Jan.
The extracellular-matrix (ECM) is a complex interconnected three-dimensional network that provides structural support for the cells and tissues and defines organ architecture as key for their healthy functioning. However, the intimate mechanisms by which ECM acquire their three-dimensional architecture are still largely unknown. In this paper, we study this question by means of a simple three-dimensional individual based model of interacting fibres able to spontaneously crosslink or unlink to each other and align at the crosslinks. We show that such systems are able to spontaneously generate different types of architectures. We provide a thorough analysis of the emerging structures by an exhaustive parametric analysis and the use of appropriate visualization tools and quantifiers in three dimensions. The most striking result is that the emergence of ordered structures can be fully explained by a single emerging variable: the number of links per fibre in the network. If validated on real tissues, this simple variable could become an important putative target to control and predict the structuring of biological tissues, to suggest possible new therapeutic strategies to restore tissue functions after disruption, and to help in the development of collagen-based scaffolds for tissue engineering. Moreover, the model reveals that the emergence of architecture is a spatially homogeneous process following a unique evolutionary path, and highlights the essential role of dynamical crosslinking in tissue structuring.
细胞外基质（ECM）是一个复杂的相互连接的三维网络，为细胞和组织提供结构支撑，并将器官结构定义为其健康功能的关键。然而，ECM形成其三维结构的具体机制在很大程度上仍不清楚。在本文中，我们通过一个简单的基于个体的三维相互作用纤维模型来研究这个问题，这些纤维能够自发地相互交联或解交联，并在交联处排列。我们表明，这样的系统能够自发地产生不同类型的结构。我们通过详尽的参数分析以及在三维空间中使用适当的可视化工具和量化指标，对所出现的结构进行了全面分析。最引人注目的结果是，有序结构的出现可以完全由一个单一的新兴变量来解释：网络中每根纤维的连接数。如果在真实组织上得到验证，这个简单的变量可能成为控制和预测生物组织结构的一个重要潜在靶点，用于提出在组织破坏后恢复组织功能的可能新治疗策略，并有助于开发用于组织工程的基于胶原蛋白的支架。此外，该模型表明，结构的出现是一个遵循独特进化路径的空间均匀过程，并突出了动态交联在组织结构形成中的重要作用。
