Tumor cells showing a 3D morphology and in coculture with endothelial cells are a valuable in vitro model for studying cell–cell interactions and for the development of pharmaceuticals. Here, we found that HepG2 cells, unlike endothelial cells, show differences in adhesion to fibronectin alone, or in combination with poly(allylamine hydrochloride). This response allowed us to engineer micropatterned heterotypic cultures of the two cell types using microfluidics to pattern cell adhesion. The resulting cocultures exhibit spatially encoded and physiologically relevant cell function. Further, we found that the protrusive, migratory and 3D morphological responses of HepG2 are synergistically modulated by the constituents of the hybrid extracellular matrix. Treating the hybrid material with the cross-linking enzyme transglutaminase inhibited 3D morphogenesis of tumor cells. Our results extend previous work on the role of fibronectin in layer-by-layer assembled films, and demonstrate that cell-specific differences in adhesion to fibronectin can be used to engineer tumor cell cocultures.

中文翻译：

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逐层组装膜中的纤连蛋白在2D和3D形态之间切换肿瘤细胞

显示3D形态并与内皮细胞共培养的肿瘤细胞是用于研究细胞间相互作用和开发药物的有价值的体外模型。在这里，我们发现与内皮细胞不同，HepG2细胞在单独或与聚烯丙胺盐酸盐联合使用时显示出对纤连蛋白的粘附差异。这种反应使我们能够使用微流控技术设计两种细胞类型的微模式异型培养物，以图案化细胞粘附。所得的共培养物表现出空间编码的和生理学相关的细胞功能。此外，我们发现HepG2的突出，迁徙和3D形态反应是由混合细胞外基质的成分协同调节的。用交联酶转谷氨酰胺酶处理杂化材料可抑制肿瘤细胞的3D形态发生。我们的研究结果扩展了先前关于纤连蛋白在逐层组装膜中的作用的工作，并证明与纤连蛋白粘附的细胞特异性差异可用于工程化肿瘤细胞共培养。