Cui Xin, Tong Jie, Yau Jimmy, Bajpai Apratim, Yang Jing, Peng Yansong, Singh Mrinalini, Qian Weiyi, Ma Xiao, Chen Weiqiang
Department of Mechanical and Aerospace Engineering, New York University, Brooklyn, New York; Department of Biomedical Engineering, New York University, Brooklyn, New York; Department of Biomedical Engineering, Jinan University, Guangzhou, China.
Department of Mechanical and Aerospace Engineering, New York University, Brooklyn, New York; Department of Biomedical Engineering, New York University, Brooklyn, New York.
Biophys J. 2020 Nov 3;119(9):1771-1780. doi: 10.1016/j.bpj.2020.09.020. Epub 2020 Sep 28.
Mechanical forces between cells and their microenvironment critically regulate the asymmetric morphogenesis and physiological functions in vascular systems. Here, we investigated the asymmetric cell alignment and cellular forces simultaneously in micropatterned endothelial cell ring-shaped sheets and studied how the traction and intercellular forces are involved in the asymmetric vascular morphogenesis. Tuning the traction and intercellular forces using different topographic geometries of symmetric and asymmetric ring-shaped patterns regulated the vascular asymmetric morphogenesis in vitro. Moreover, pharmacologically suppressing the cell traction force and intercellular force disturbed the force-dependent asymmetric cell alignment. We further studied this phenomenon by modeling the vascular sheets with a mechanical force-propelled active particle model and confirmed that mechanical forces synergistically drive the asymmetric endothelial cell alignments in different tissue geometries. Further study using mouse diabetic aortic endothelial cells indicated that diseased endothelial cells exhibited abnormal cell alignments, traction, and intercellular forces, indicating the importance of mechanical forces in physiological vascular morphogenesis and functions. Overall, we have established a controllable micromechanical platform to study the force-dependent vascular asymmetric morphogenesis and thus provide a direct link between single-cell mechanical processes and collective behaviors in a multicellular environment.
细胞与其微环境之间的机械力对血管系统中的不对称形态发生和生理功能起着至关重要的调节作用。在此，我们同时研究了微图案化内皮细胞环形片层中的不对称细胞排列和细胞力，并探讨了牵引力和细胞间力如何参与不对称血管形态发生。利用对称和不对称环形图案的不同地形几何形状调节牵引力和细胞间力，在体外调控了血管不对称形态发生。此外，通过药理学方法抑制细胞牵引力和细胞间力会扰乱力依赖性不对称细胞排列。我们通过用机械力驱动的活性粒子模型对血管片层进行建模进一步研究了这一现象，并证实机械力在不同组织几何形状中协同驱动不对称内皮细胞排列。使用小鼠糖尿病主动脉内皮细胞的进一步研究表明，患病内皮细胞表现出异常的细胞排列、牵引力和细胞间力，这表明机械力在生理性血管形态发生和功能中的重要性。总体而言，我们建立了一个可控的微机械平台来研究力依赖性血管不对称形态发生，从而在多细胞环境中为单细胞机械过程与集体行为之间提供了直接联系。
