Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments.
Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments.
复制标题
细胞介导的纤维募集驱动工程原纤维微环境中的细胞外基质机械感应。
DOI：
10.1038/nmat4444
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发表时间：
2015-12
期刊：
影响因子：
41.2
通讯作者：
Chen CS
中科院分区：
文献类型：
--
作者：
Baker BM;Trappmann B;Wang WY;Sakar MS;Kim IL;Shenoy VB;Burdick JA;Chen CS
为了研究细胞如何在结构类似于天然细胞外基质(ECM)的环境中感知硬度，我们设计了一种具有可调机械结构和用户定义结构的合成纤维材料。与平坦的水凝胶表面相比，这些纤维材料重现了观察到的细胞-基质与胶原基质的相互作用，包括星状细胞形态、细胞介导的纤维重排和材料的整体收缩。增加平坦水凝胶表面的硬度会促进间充质干细胞的扩散和增殖，而增加纤维的硬度反而会抑制铺展和增殖，这取决于网络结构。较低的纤维硬度允许活跃的细胞力招募附近的纤维，动态增加细胞表面的配体密度，促进局部粘连和相关信号的形成。这些研究表明，与水凝胶表面建立的材料硬度和铺展之间的良好关系不同，并引入了纤维募集作为细胞探测和响应纤维基质中的力学的一种新机制。
To investigate how cells sense stiffness in settings structurally similar to native extracellular matrices (ECM), we designed a synthetic fibrous material with tunable mechanics and user-defined architecture. In contrast to flat hydrogel surfaces, these fibrous materials recapitulated cell-matrix interactions observed with collagen matrices including stellate cell morphologies, cell-mediated realignment of fibers, and bulk contraction of the material. While increasing the stiffness of flat hydrogel surfaces induced mesenchymal stem cell spreading and proliferation, increasing fiber stiffness instead suppressed spreading and proliferation depending on network architecture. Lower fiber stiffness permitted active cellular forces to recruit nearby fibers, dynamically increasing ligand density at the cell surface and promoting the formation of focal adhesions and related signaling. These studies demonstrate a departure from the well-described relationship between material stiffness and spreading established with hydrogel surfaces, and introduce fiber recruitment as a novel mechanism by which cells probe and respond to mechanics in fibrillar matrices.