Synthetic hydrogels with controlled physicochemical matrix properties serve as powerful in vitro tools to dissect cell-extracellular matrix (ECM) interactions that regulate epithelial morphogenesis in 3D microenvironments. In addition, these fully defined matrices overcome the lot-to-lot variability of naturally derived materials and have provided insights into the formation of rudimentary epithelial organs. Therefore, we engineered a fully defined synthetic hydrogel with independent control over proteolytic degradation, mechanical properties, and adhesive ligand type and density to study the impact of ECM properties on epithelial tubulogenesis for inner medullary collecting duct (IMCD) cells. Protease sensitivity of the synthetic material for membrane-type matrix metalloproteinase-1 (MT1-MMP, also known as MMP14) was required for tubulogenesis. Additionally, a defined range of matrix elasticity and presentation of RGD adhesive peptide at a threshold level of 2 mM ligand density were required for epithelial tubulogenesis. Finally, we demonstrated that the engineered hydrogel supported organization of epithelial tubules with a lumen and secreted laminin. This synthetic hydrogel serves as a platform that supports epithelial tubular morphogenetic programs and can be tuned to identify ECM biophysical and biochemical properties required for epithelial tubulogenesis.

中文翻译：

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通过使用合成水凝胶鉴定肾上皮细胞微管形成所需的基质理化性质。

具有可控的理化基质特性的合成水凝胶可作为强大的体外工具来剖析调节3D微环境中上皮形态发生的细胞-细胞外基质（ECM）相互作用。此外，这些完全定义的矩阵克服了天然衍生材料的批次差异，并提供了对原始上皮器官形成的见解。因此，我们设计了一种完全定义的合成水凝胶，可以独立控制蛋白水解降解，机械性能以及粘附配体的类型和密度，以研究ECM特性对髓内集管（IMCD）细胞上皮小管生成的影响。合成材料对膜型基质金属蛋白酶-1（MT1-MMP，也称为MMP14）的蛋白酶敏感性是形成小管的必要条件。另外，上皮肾小管生成需要基质弹性的限定范围和RGD粘附肽在2 mM配体密度的阈值水平下的呈递。最后，我们证明了工程水凝胶支持具有内腔和分泌层粘连蛋白的上皮小管的组织。这种合成水凝胶可作为支持上皮肾小管形态发生程序的平台，并可进行调整以识别上皮微管发生所需的ECM生物物理和生化特性。