Role of material-driven fibronectin fibrillogenesis in cell differentiation
Role of material-driven fibronectin fibrillogenesis in cell differentiation
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DOI：
10.1016/j.biomaterials.2010.11.057
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发表时间：
2011-03-01
期刊：
影响因子：
14
通讯作者：
Garcia, Andres J.
中科院分区：
文献类型：
--
作者：
Salmeron-Sanchez, Manuel;Rico, Patricia;Garcia, Andres J.
纤连蛋白 (FN) 是一种普遍存在的细胞外基质蛋白 (ECM) 蛋白，细胞通过涉及收缩力的整合素介导的过程将其组织成纤维网络。这种组装允许 FN 分子展开，暴露天然球状 FN 结构中不存在的隐秘结构域并激活细胞内信号传导复合物。然而，尚未观察到 FN 在吸附到材料表面后组织成生理纤维网络。在这里，我们展示了无细胞、材料诱导的 FN 纤维形成为具有增强细胞活性的生物基质。我们发现，简单的 FN 吸附到聚（丙烯酸乙酯）表面（而不是对照聚合物），通过氨基末端 70 kDa 片段的相互作用触发 FN 组织成纤维网络，该片段参与细胞介导的 FN 纤维的形成。此外，与单个 FN 分子甚至 I 型胶原相比，材料驱动的 FN 原纤维在生肌分化方面表现出增强的生物活性。我们的结果表明，FN 的分子组装可以在材料界面发生，从而产生类似于细胞组装的纤维状基质的生理蛋白质网络。这项研究确定了触发细胞外基质蛋白组织成生物活性原纤维的材料表面，并建立了设计 ECM 模拟生物材料的新范例。 (C) 2010 Elsevier Ltd. 保留所有权利。
Fibronectin (FN) is a ubiquitous extracellular matrix protein (ECM) protein that is organized into fibrillar networks by cells through an integrin-mediated process that involves contractile forces. This assembly allows for the unfolding of the FN molecule, exposing cryptic domains that are not available in the native globular FN structure and activating intracellular signalling complexes. However, organization of FN into a physiological fibrillar network upon adsorption on a material surface has not been observed. Here we demonstrate cell-free, material-induced FN fibrillogenesis into a biological matrix with enhanced cellular activities. We found that simple FN adsorption onto poly(ethyl acrylate) surfaces, but not control polymers, triggered FN organization into a fibrillar network via interactions in the amino-terminal 70 kDa fragment, which is involved in the formation of cell-mediated FN fibrils. Moreover, the material-driven FN fibrils exhibited enhanced biological activities in terms of myogenic differentiation compared to individual FN molecules and even type I collagen. Our results demonstrate that molecular assembly of FN can take place at the material interface, giving rise to a physiological protein network similar to fibrillar matrices assembled by cells. This research identifies material surfaces that trigger the organization of extracellular matrix proteins into biological active fibrils and establishes a new paradigm to engineer ECM-mimetic biomaterials. (C) 2010 Elsevier Ltd. All rights reserved.