Fibronectin fibril alignment is established upon initiation of extracellular matrix assembly.
Fibronectin fibril alignment is established upon initiation of extracellular matrix assembly.
复制标题
纤连蛋白原纤维排列在细胞外基质组装开始时建立。
DOI：
10.1091/mbc.e20-08-0533
复制
发表时间：
2021-04-15
影响因子：
3.3
通讯作者：
Schwarzbauer JE
中科院分区：
文献类型：
--
作者：
Garrison CM;Schwarzbauer JE
细胞外基质(ECM)的物理结构是组织特有的，是正常组织功能的基础。ECM纤维的正确排列对各种组织的功能至关重要。虽然基质组装总体上已被深入研究，但对形成排列整齐的ECM纤维所需的机制知之甚少。我们研究了使用平行ECM纤维的成纤维细胞启动纤维连接蛋白(FN)基质组装的过程，发现启动FN纤维形成的基质组装位置平行地定向在细胞极点。我们发现，这些极化的基质组装部位会发展成纤维粘连，最终形成排列的FN纤维。组装未对齐的网络基质的细胞在细胞外围形成基质组装部位，但这些细胞中基质组装部位的分布可以通过微图案化或机械拉伸来调节。虽然细长的细胞形状对应于极化的基质组装位点分布，但这两个特征并不是绝对联系的，因为我们发现转化生长因子β(转化生长因子-β1)独立于细胞伸长增强基质组装位点的极性和排列的纤维的组装。我们得出结论，FN纤维的最终取向是由细胞-FN相互作用初期形成的基质组装部位的排列和分布决定的。
The physical structure of the extracellular matrix (ECM) is tissue-specific and fundamental to normal tissue function. Proper alignment of ECM fibers is essential for the functioning of a variety of tissues. While matrix assembly in general has been intensively investigated, little is known about the mechanisms required for formation of aligned ECM fibrils. We investigated the initiation of fibronectin (FN) matrix assembly using fibroblasts that assemble parallel ECM fibrils and found that matrix assembly sites, where FN fibrillogenesis is initiated, were oriented in parallel at the cell poles. We show that these polarized matrix assembly sites progress into fibrillar adhesions and ultimately into aligned FN fibrils. Cells that assemble an unaligned meshwork matrix form matrix assembly sites around the cell periphery, but the distribution of matrix assembly sites in these cells could be modulated through micropatterning or mechanical stretch. While an elongated cell shape corresponds with a polarized matrix assembly site distribution, these two features are not absolutely linked, since we discovered that transforming growth factor beta (TGF-β1) enhances matrix assembly site polarity and assembly of aligned fibrils independent of cell elongation. We conclude that the ultimate orientation of FN fibrils is determined by the alignment and distribution of matrix assembly sites that form during the initial stages of cell–FN interactions.