Modeling collagen fibril self-assembly from extracellular medium in embryonic tendon.
Modeling collagen fibril self-assembly from extracellular medium in embryonic tendon.
复制标题
胚胎肌腱细胞外介质中胶原纤维自组装的建模。
DOI：
10.1016/j.bpj.2023.07.001
复制
发表时间：
2023
影响因子：
3.4
通讯作者：
Revell CK
中科院分区：
文献类型：
--
作者：
Revell CK
胶原蛋白是多细胞生物体的关键结构成分，并且以高度组织化的方式排列。在肌腱等结构组织中，胶原蛋白在细胞之间形成平行纤维束，这些纤维出现在小鼠胚胎发育期间胚胎第13.5天（E13.5）和E14.5之间的24小时窗口内。目前的模型假设胶原的组织结构需要直接的细胞控制，从而细胞主动地从细胞表面沉积胶原原纤维。然而，这样的模型似乎与原纤维形成的时间和长度尺度不相容。我们提出了一个相变模型来解释胚胎肌腱中有序原纤维的快速发育，从而减少对活跃细胞过程的依赖。我们开发的相场晶体模拟的胶原原纤维形成的领域来自胚胎肌腱细胞间的空间的电子显微镜照片和比较结果定性和定量观察到的原纤维形成的模式。为了测试这个相变模型的预测，即游离的原聚体胶原蛋白应该存在于细胞间的空间之前，形成可观察到的原纤维，我们使用激光捕获显微切割，再加上质谱，这表明稳定增加的游离胶原蛋白在细胞间的空间高达E13.5，随后由一个快速减少的游离胶原蛋白，符合外观的可溶性较低的胶原蛋白原纤维。模型和测量一起提供了证据，在胚胎小鼠肌腱的胶原纤维的细胞外自组装，支持在胚胎发育过程中快速胶原纤维形成的额外机制。
Collagen is a key structural component of multicellular organisms and is arranged in a highly organized manner. In structural tissues such as tendons, collagen forms bundles of parallel fibers between cells, which appear within a 24-h window between embryonic day 13.5 (E13.5) and E14.5 during mouse embryonic development. Current models assume that the organized structure of collagen requires direct cellular control, whereby cells actively lay down collagen fibrils from cell surfaces. However, such models appear incompatible with the time and length scales of fibril formation. We propose a phase-transition model to account for the rapid development of ordered fibrils in embryonic tendon, reducing reliance on active cellular processes. We develop phase-field crystal simulations of collagen fibrillogenesis in domains derived from electron micrographs of inter-cellular spaces in embryonic tendon and compare results qualitatively and quantitatively to observed patterns of fibril formation. To test the prediction of this phase-transition model that free protomeric collagen should exist in the inter-cellular spaces before the formation of observable fibrils, we use laser-capture microdissection, coupled with mass spectrometry, which demonstrates steadily increasing free collagen in inter-cellular spaces up to E13.5, followed by a rapid reduction of free collagen that coincides with the appearance of less-soluble collagen fibrils. The model and measurements together provide evidence for extracellular self-assembly of collagen fibrils in embryonic mouse tendon, supporting an additional mechanism for rapid collagen fibril formation during embryonic development.