Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix.
Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix.
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DOI：
10.1038/ncomms9026
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发表时间：
2015-08-14
影响因子：
16.6
通讯作者：
Vogel V
中科院分区：
文献类型：
--
作者：
Kubow KE;Vukmirovic R;Zhe L;Klotzsch E;Smith ML;Gourdon D;Luna S;Vogel V
尽管细胞外基质(ECM)在指导健康和疾病组织中的细胞命运-特别是在发育、伤口愈合、组织再生和癌症中发挥着关键作用-但指导ECM组装和调节ECM的分级结构的机制尚不清楚。I型胶原基质在体内的组装需要细胞活化的纤维连接蛋白(FN)纤维生成。在这里，我们使用FN-FRET探针作为机械应变传感器，并证明在细胞培养中，I型胶原纤维优先与更松弛的FN纤维共存于成纤维细胞的ECM中。纤维拉伸分析研究表明，I型胶原的FN结合域负责机械调节的相互作用。此外，我们还发现纤维连接蛋白与胶原之间的相互作用是相互作用的：松弛的纤维连接纤维作为胶原蛋白组装的多价模板，但一旦组装，胶原纤维就能保护纤维连接不被细胞牵引力拉伸。因此，除了公认的、受力调节的细胞-基质相互作用外，力还调节不同结构的ECM组件之间的相互作用。胶原细胞外基质的组装需要纤维连接蛋白的存在，但指导这种组装的机制尚不清楚。在这里，作者表明，I型胶原使用松弛的纤维连接蛋白纤维作为组装的模板，进而保护纤维连接蛋白纤维不受力介导的拉伸。
Despite the crucial role of extracellular matrix (ECM) in directing cell fate in healthy and diseased tissues—particularly in development, wound healing, tissue regeneration and cancer—the mechanisms that direct the assembly and regulate hierarchical architectures of ECM are poorly understood. Collagen I matrix assembly in vivo requires active fibronectin (Fn) fibrillogenesis by cells. Here we exploit Fn-FRET probes as mechanical strain sensors and demonstrate that collagen I fibres preferentially co-localize with more-relaxed Fn fibrils in the ECM of fibroblasts in cell culture. Fibre stretch-assay studies reveal that collagen I's Fn-binding domain is responsible for the mechano-regulated interaction. Furthermore, we show that Fn-collagen interactions are reciprocal: relaxed Fn fibrils act as multivalent templates for collagen assembly, but once assembled, collagen fibres shield Fn fibres from being stretched by cellular traction forces. Thus, in addition to the well-recognized, force-regulated, cell-matrix interactions, forces also tune the interactions between different structural ECM components. Assembly of a collagen extracellular matrix requires the presence of fibronectin, but the mechanisms that direct this assembly are not known. Here the authors show that collagen I uses relaxed fibronectin fibrils as a template for assembly, and in turn shield fibronectin fibrils from force-mediated stretching.