Center for Biomaterials and Tissue Engineering, Universidad Politécnica de Valencia, Spain.
Biomaterials. 2011 Mar;32(8):2099-105. doi: 10.1016/j.biomaterials.2010.11.057. Epub 2010 Dec 24.
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.
纤连蛋白（FN）是一种普遍存在的细胞外基质蛋白（ECM），通过整合素介导的过程，细胞将其组织成纤维状网络，该过程涉及收缩力。这种组装允许 FN 分子展开，暴露出在天然球形 FN 结构中不可用的隐藏结构域，并激活细胞内信号复合物。然而，在材料表面上吸附时，FN 并未形成生理纤维网络。在这里，我们证明了无细胞的、材料诱导的 FN 原纤维形成，形成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，但不是对照聚合物，通过涉及细胞介导的 FN 原纤维形成的氨基末端 70 kDa 片段的相互作用，触发 FN 组织成纤维网络。此外，与单个 FN 分子甚至 I 型胶原相比，材料驱动的 FN 原纤维在肌生成分化方面表现出增强的生物学活性。我们的结果表明，FN 的分子组装可以在材料界面发生，形成类似于细胞组装的生理蛋白网络。该研究确定了触发细胞外基质蛋白组织成生物活性纤维的材料表面，并建立了一种新的范例来工程 ECM 模拟生物材料。
