Wong Hua, Crowet Jean-Marc, Dauchez Manuel, Ricard-Blum Sylvie, Baud Stéphanie, Belloy Nicolas
Université de Reims Champagne Ardenne, CNRS, MEDyC UMR 7369, 51097 Reims, France.
Univ. Lyon, University Claude Bernard Lyon 1, ICBMS, UMR 5246 CNRS, 69622 Villeurbanne Cedex, France.
Matrix Biol Plus. 2021 Dec 14;13:100096. doi: 10.1016/j.mbplus.2021.100096. eCollection 2022 Feb.
The extracellular matrix is a complex three-dimensional network of molecules that provides cells with a complex microenvironment. The major constituents of the extracellular matrix such as collagen, elastin and associated proteins form supramolecular assemblies contributing to its physicochemical properties and organization. The structure of proteins and their supramolecular assemblies such as fibrils have been studied at the atomic level (e.g., by X-ray crystallography, Nuclear Magnetic Resonance and cryo-Electron Microscopy) or at the microscopic scale. However, many protein complexes are too large to be studied at the atomic level and too small to be studied by microscopy. Most extracellular matrix components fall into this intermediate scale, so-called the mesoscopic scale, preventing their detailed characterization. Simulation and modelling are some of the few powerful and promising approaches that can deepen our understanding of mesoscale systems. We have developed a set of modelling tools to study the self-organization of the extracellular matrix and large motion of macromolecules at the mesoscale level by taking advantage of the dynamics of articulated rigid bodies as a mean to study a larger range of motions at the cost of atomic resolution.
细胞外基质是一个复杂的三维分子网络，为细胞提供复杂的微环境。细胞外基质的主要成分，如胶原蛋白、弹性蛋白及相关蛋白，形成超分子聚集体，赋予其物理化学性质和组织结构。蛋白质及其超分子聚集体（如原纤维）的结构已在原子水平（如通过X射线晶体学、核磁共振和冷冻电子显微镜）或微观尺度上进行了研究。然而，许多蛋白质复合物太大，无法在原子水平上进行研究，又太小，无法通过显微镜进行研究。大多数细胞外基质成分都属于这种中间尺度，即所谓的介观尺度，这使得它们无法得到详细的表征。模拟和建模是少数几种强大且有前景的方法，能够加深我们对介观系统的理解。我们开发了一套建模工具，通过利用关节刚体动力学，以牺牲原子分辨率为代价来研究更大范围的运动，从而在介观水平上研究细胞外基质的自组装和大分子的大尺度运动。
