Stimulatory effects of a three-dimensional microenvironment on cell-mediated fibronectin fibrillogenesis
Stimulatory effects of a three-dimensional microenvironment on cell-mediated fibronectin fibrillogenesis
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DOI：
10.1242/jcs.02566
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发表时间：
2005-10-01
影响因子：
4
通讯作者：
Schwarzbauer, JE
中科院分区：
文献类型：
--
作者：
Mao, Y;Schwarzbauer, JE
纤连蛋白组装成纤维状基质是一个受调节的逐步过程，涉及与整合素受体的结合以及纤连蛋白分子之间的相互作用。已使用二维 (2D) 单层培养细胞对该过程进行了广泛研究。然而，在体内的大多数情况下，基质组装发生在现有的三维 (3D) 细胞外基质网络内。为了模拟这种环境，我们分析了在预组装的 3D 纤连蛋白基质上培养的成纤维细胞的基质组装，发现与 2D 培养中的细胞相比，纤连蛋白原纤维组装受到显着刺激。启动组装过程所需的纤连蛋白量较少，原纤维积累到更高的密度，并且 3D 原纤维组织在刺激效果中发挥了关键作用。此外，表达激活依赖性整合素的细胞能够在没有外源刺激的情况下组装纤连蛋白基质，这表明3D纤连蛋白基质对整合素活性的调节作用。这些结果为通过细胞与局部微环境的相互作用来额外控制纤连蛋白沉积提供了证据。
The assembly of fibronectin into a fibrillar matrix is a regulated step-wise process that involves binding to integrin receptors and interactions between fibronectin molecules. This process has been studied extensively using cells in two-dimensional (2D) monolayer culture. In most situations in vivo, however, matrix assembly occurs within existing three-dimensional (3D) extracellular matrix networks. In an attempt to mimic this environment, we analyzed matrix assembly by fibroblasts cultured on a pre-assembled 3D fibronectin matrix and found significant stimulation of fibronectin fibril assembly compared to cells in 2D culture. Lower amounts of fibronectin were needed to initiate the assembly process, fibrils accumulated to higher density, and the 3D fibril organization played a key role in the stimulatory effect. Moreover, cells expressing activation-dependent integrins were able to assemble fibronectin matrix without exogenous stimulation, suggesting regulatory effects of the 3D fibronectin matrix on integrin activity. These results provide evidence for an additional level of control of fibronectin deposition through cell interactions with the local microenvironment.