Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
School of Mechanical & Aerospace Engineering, Nanyang Technological University, Singapore.
Acta Biomater. 2022 Apr 1;142:149-159. doi: 10.1016/j.actbio.2022.01.057. Epub 2022 Feb 4.
The propensity of cells to align in particular directions is relevant to a number of areas, including tissue engineering and biohybrid robotics. Cell alignment is modulated through various extracellular conditions including surface topographies, mechanical cues from cell-matrix interactions, and cell-cell interactions. Understanding of these conditions provides guidance for desirable cellular structure constructions. In this study, we examine the roles of surface topographies and cell-cell interactions in inducing cell alignment. We employed wavy surface topographies at the nanometer scale as a model extracellular environment for cell culture. The results show that, within a certain range of wavelengths and amplitudes of the surface topographies, cell alignment is dependent on cell confluency. This dependence on both topology and confluency suggests interplay between cell-cell and cell-matrix interactions in inducing cell alignment. Images of sparsely distributed and confluent cells also demonstrated clear differences in the structures of their focal adhesion complexes. To understand this effect, we introduced anti-N-cadherin to cell culture to inhibit cell-cell interactions. The results show that, when anti-N-cadherin was applied, cells on wavy surfaces required greater confluency to achieve the same alignment compared to that in the absence of anti-N-cadherin. The understanding of the cell alignment mechanisms will be important in numerous potential applications such as scaffold design, tissue repair, and development of biohybrid robotic systems. STATEMENT OF SIGNIFICANCE: Cell alignment plays a critical role in numerous biological functions. Advances in tissue engineering utilizes cell alignment to restore, maintain, or even replace different types of biological tissues. The clinical impact that tissue engineering has made is facilitated by advancements in the understanding of interactions between scaffolds, biological factors, and cells. This work further elucidates the role of cell-cell interactions in promoting the organization of biological tissues.
细胞在特定方向上排列的倾向与许多领域相关，包括组织工程和生物混合机器人学。细胞排列通过各种细胞外条件进行调节，包括表面形貌、细胞-基质相互作用的机械线索以及细胞-细胞相互作用。对这些条件的理解为理想的细胞结构构建提供了指导。在这项研究中，我们研究了表面形貌和细胞-细胞相互作用在诱导细胞排列中的作用。我们采用纳米级的波浪形表面形貌作为细胞培养的模型细胞外环境。结果表明，在表面形貌的波长和振幅一定范围内，细胞排列取决于细胞融合度。这种对拓扑结构和融合度的依赖性表明，细胞-细胞相互作用和细胞-基质相互作用在诱导细胞排列中相互作用。稀疏分布和融合细胞的图像也显示了其焦点粘连复合物结构的明显差异。为了理解这种效应，我们将抗 N-钙粘蛋白引入细胞培养以抑制细胞-细胞相互作用。结果表明，当应用抗 N-钙粘蛋白时，与不存在抗 N-钙粘蛋白相比，波浪表面上的细胞需要更高的融合度才能达到相同的排列。对细胞排列机制的理解将在许多潜在应用中非常重要，例如支架设计、组织修复和生物混合机器人系统的开发。
细胞排列在许多生物学功能中起着关键作用。组织工程的进步利用细胞排列来恢复、维持甚至替代不同类型的生物组织。组织工程所产生的临床影响得益于对支架、生物因素和细胞之间相互作用的理解的进步。这项工作进一步阐明了细胞-细胞相互作用在促进生物组织组织方面的作用。
