Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea; School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
Acta Biomater. 2018 Sep 1;77:311-321. doi: 10.1016/j.actbio.2018.07.019. Epub 2018 Jul 11.
The unique structure of kidney tubules is representative of their specialized function. Because maintaining tubular structure and controlled diameter is critical for kidney function, it is critical to understand how topographical cues, such as curvature, might alter cell morphology and biological characteristics. Here, we examined the effect of substrate curvature on the shape and phenotype of two kinds of renal epithelial cells (MDCK and HK-2) cultured on a microchannel with a broad range of principal curvature. We found that cellular architecture on curved substrates was closely related to the cell type-specific characteristics (stiffness, cell-cell adherence) of the cells and their density, as well as the sign and degree of curvature. As the curvature increased on convex channels, HK-2 cells, having lower cell stiffness and monolayer integrity than those of MDCK cells, aligned their in-plane axis perpendicular to the channel but did not significantly change in morphology. By contrast, MDCK cells showed minimal change in both morphology and alignment. However, on concave channels, both cell types were elongated and showed longitudinal directionality, although the changes in MDCK cells were more conservative. Moreover, substrate curvature contributed to cell polarization by enhancing the expression of apical and basolateral cell markers with height increase of the cells. Our study suggests curvature to be an important guiding principle for advanced tissue model developments, and that curved and geometrically ambiguous substrates can modulate the cellular morphology and phenotype.
In many tissues, such as renal tubules or intestinal villi, epithelial layers exist in naturally curved forms, a geometry that is not reproduced by flat cultures. Because maintaining tubular structure is critical for kidney function, it is important to understand how topographical cues, such as curvature, might alter cell morphology and biological characteristics. We found that cellular architecture on curved substrates was closely related to cell type and density, as well as the sign and degree of the curvature. Moreover, substrate curvature contributed to cell polarization by enhancing the expression of apical and basolateral cell markers with height increase. Our results suggested that substrate curvature might contribute to cellular architecture and enhance the polarization of kidney tubule cells.
肾单位独特的结构是其特殊功能的代表。由于维持管状结构和控制直径对肾功能至关重要，因此了解地形线索（如曲率）如何改变细胞形态和生物学特性非常重要。在这里，我们研究了基底曲率对两种肾上皮细胞（MDCK 和 HK-2）在具有广泛主曲率的微通道上的形状和表型的影响。我们发现，弯曲基底上的细胞结构与细胞类型特异性特征（刚性、细胞间黏附）、细胞密度以及曲率的符号和程度密切相关。随着凸通道上曲率的增加，HK-2 细胞的刚性和单层完整性低于 MDCK 细胞，它们将平面轴垂直于通道排列，但形态上没有明显变化。相比之下，MDCK 细胞在形态和排列上变化都很小。然而，在凹通道上，两种细胞类型都被拉长并呈现纵向方向，尽管 MDCK 细胞的变化更为保守。此外，基底曲率通过增强细胞标志物的表达促进细胞极化，随着细胞高度的增加，细胞标志物向顶端和基底外侧表达。我们的研究表明，曲率是先进组织模型发展的重要指导原则，弯曲和几何上不确定的基底可以调节细胞形态和表型。
在许多组织中，如肾小管或肠绒毛，上皮层以自然弯曲的形式存在，而这种几何形状在平面培养中无法再现。由于维持管状结构对肾功能至关重要，因此了解地形线索（如曲率）如何改变细胞形态和生物学特性非常重要。我们发现，弯曲基底上的细胞结构与细胞类型和密度密切相关，以及曲率的符号和程度。此外，基底曲率通过增强细胞标志物的表达促进细胞极化，随着细胞高度的增加，细胞标志物向顶端和基底外侧表达。我们的结果表明，基底曲率可能有助于细胞结构并增强肾小管细胞的极化。
