Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Center for Biotechnology and Interdisciplinary Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Center for Modeling, Simulation, and Imaging in Medicine, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
J Biomech. 2023 Jan;147:111435. doi: 10.1016/j.jbiomech.2023.111435. Epub 2023 Jan 5.
Internal organs such as the heart demonstrate apparent left-right (LR) asymmetric morphology and positioning. Cellular chirality and associated LR biased mechanical behavior such as cell migration have been attributed to LR symmetry breaking during embryonic development. Mathematical models have shown that chiral directional migration can be driven by cellular intrinsic torque. Tissue jamming state (i.e., solid-like vs fluid-like state) strongly regulates collective migratory behavior, but how it might affect chiral morphogenesis is still unknown. Here, we develop a cell vertex model to study the role of tissue rigidity or jamming state on chiral morphogenesis of the cells on a patterned ring-shaped tissue, simulating a previously reported experimental setup for measuring cell chirality. We simulate chirality as torsional forces acting on cell vertices. As expected, the cells undergo bidirectional migration at the opposing (inner and outer) boundaries of the ring-shaped tissue. We discover that more fluid-like tissues (unjammed) demonstrate a stronger chiral cell alignment and elongation than more solid-like (jammed) tissues and maintain a bigger difference in migration velocity between opposing tissue boundaries. Finally, we find that fluid-like tissues undergo more cell-neighbor exchange events. This study reveals that chiral torque is sufficient to achieve a biased cellular alignment as seen in vitro. It further sheds light on the mechanical regulation of chiral morphogenesis of tissues and reveals a role of cell density-independent tissue rigidity in this process.
内部器官如心脏表现出明显的左右(LR)不对称形态和定位。细胞手性和相关的 LR 偏置机械行为,如细胞迁移,归因于胚胎发育过程中的 LR 对称破缺。数学模型表明,手性定向迁移可以由细胞内在的扭矩驱动。组织堵塞状态(即固态与液态状态)强烈调节集体迁移行为,但它如何影响手性形态发生仍然未知。在这里,我们开发了一个细胞顶点模型来研究组织刚性或堵塞状态对细胞在图案化环形组织上的手性形态发生的作用,模拟了以前报道的用于测量细胞手性的实验设置。我们将手性模拟为作用于细胞顶点的扭转力。正如预期的那样,细胞在环形组织的相对(内和外)边界处进行双向迁移。我们发现,更类似流体的组织(未堵塞)表现出比更类似固体的组织(堵塞)更强的手性细胞排列和伸长,并保持在相对组织边界处的迁移速度差异更大。最后,我们发现类似流体的组织经历更多的细胞邻居交换事件。这项研究表明,手性扭矩足以实现体外观察到的偏向性细胞排列。它进一步揭示了组织手性形态发生的机械调节,并揭示了细胞密度独立的组织刚性在这个过程中的作用。