Chen Jianfeng, Chen Xuefei, Ma Yihao, Liu Yiran, Li Jin, Peng Kai, Dai Yichuan, Chen Xiaoxiao
School of Advanced Manufacturing, Nanchang University, Nanchang 330031, Jiangxi, P. R. China.
ACS Omega. 2023 Oct 27;8(44):41374-41382. doi: 10.1021/acsomega.3c04981. eCollection 2023 Nov 7.
Extensive research has been conducted to examine how substrate topological factors are involved in modulating the cell behavior. Among numerous topological factors, the vital influence of the touchable depth of substrates on cell behaviors has already been extensively characterized, but the response of cells to the topological structure at untouchable depth is still elusive. Herein, the influences of substrate depth on myoblast behaviors are systematically investigated using substrates with depths ranging from touchable depth (microgrooved) to untouchable depth (microbridges). The results show that an increase in microgroove depth is accompanied by an inhibited cell spreading, an enhanced elongation, and a more obvious orientation along microgrooves. Interestingly, myoblasts located on microbridges show a more pronounced elongation with increasing culture time but a position-dependent orientation. Myoblasts on the center and parallel boundary of microbridges orient along the bridges, while myoblasts on the vertical boundary align perpendicular to the microbridges. Moreover, the differentiation results of the myoblasts indicate that the differentiated myotubes can maintain this position-dependent orientation. The simulation of the stress field in cell monolayers suggests that the position-dependent orientation is caused by the comprehensive response of myoblasts to the substrate discontinuity and substrate depth. These findings provide valuable insights into the mechanism of cell depth sensing and could inform the design of tissue engineering scaffolds for skeletal muscle and biohybrid actuation.
已经开展了广泛的研究来考察底物拓扑因素如何参与调节细胞行为。在众多拓扑因素中，底物可触及深度对细胞行为的重要影响已得到广泛表征，但细胞对不可触及深度处拓扑结构的反应仍不清楚。在此，使用从可触及深度（微槽）到不可触及深度（微桥）的不同深度的底物，系统地研究了底物深度对成肌细胞行为的影响。结果表明，微槽深度增加伴随着细胞铺展受到抑制、伸长增强以及沿微槽方向更明显的定向。有趣的是，位于微桥上的成肌细胞随着培养时间的增加显示出更明显的伸长，但定向具有位置依赖性。微桥中心和平行边界上的成肌细胞沿桥定向，而垂直边界上的成肌细胞垂直于微桥排列。此外，成肌细胞的分化结果表明，分化的肌管可以维持这种位置依赖性定向。细胞单层应力场的模拟表明，位置依赖性定向是由成肌细胞对底物不连续性和底物深度的综合反应引起的。这些发现为细胞深度感知机制提供了有价值的见解，并可为骨骼肌组织工程支架和生物杂交驱动的设计提供参考。
