Zhou Lüwen, Feng Shiliang, Li Long, Lü Shouqin, Zhang Yan, Long Mian
Smart Materials and Advanced Structure Laboratory, School of Mechanical Engineering and Mechanics, Ningbo University, Ningbo Zhejiang, China.
Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
Front Cell Dev Biol. 2021 Nov 17;9:786254. doi: 10.3389/fcell.2021.786254. eCollection 2021.
Many eukaryotic cells, including neutrophils and cells, are able to undergo correlated random migration in the absence of directional cues while reacting to shallow gradients of chemoattractants with exquisite precision. Although progress has been made with regard to molecular identities, it remains elusive how molecular mechanics are integrated with cell mechanics to initiate and manipulate cell motility. Here, we propose a two dimensional (2D) cell migration model wherein a multilayered dynamic seesaw mechanism is accompanied by a mechanical strain-based inhibition mechanism. In biology, these two mechanisms can be mapped onto the biochemical feedback between phosphoinositides (PIs) and Rho GTPase and the mechanical interplay between filamin A (FLNa) and FilGAP. Cell migration and the accompanying morphological changes are demonstrated in numerical simulations using a particle-spring model, and the diffusion in the cell membrane are simulations using a one dimensional (1D) finite differences method (FDM). The fine balance established between endogenous signaling and a mechanically governed inactivation scheme ensures the endogenous cycle of self-organizing pseudopods, accounting for the correlated random migration. Furthermore, this model cell manifests directional and adaptable responses to shallow graded signaling, depending on the overwhelming effect of the graded stimuli guidance on strain-based inhibition. Finally, the model cell becomes trapped within an obstacle-ridden spatial region, manifesting a shuttle run for local explorations and can chemotactically "escape", illustrating again the balance required in the complementary signaling pathways.
许多真核细胞，包括中性粒细胞等，在没有定向线索的情况下能够进行相关的随机迁移，同时又能极其精确地对趋化因子的浅梯度做出反应。尽管在分子识别方面已经取得了进展，但分子机制如何与细胞力学整合以启动和操纵细胞运动性仍然难以捉摸。在这里，我们提出了一种二维（2D）细胞迁移模型，其中多层动态跷跷板机制伴随着基于机械应变的抑制机制。在生物学中，这两种机制可以映射到磷酸肌醇（PIs）和Rho GTPase之间的生化反馈以及细丝蛋白A（FLNa）和FilGAP之间的机械相互作用上。使用粒子弹簧模型在数值模拟中展示了细胞迁移及伴随的形态变化，使用一维（1D）有限差分法（FDM）对细胞膜中的扩散进行了模拟。内源性信号传导与机械控制的失活机制之间建立的精细平衡确保了自组织伪足的内源性循环，解释了相关的随机迁移。此外，根据梯度刺激引导对基于应变的抑制的压倒性影响，该模型细胞对浅梯度信号表现出定向和适应性反应。最后，模型细胞被困在充满障碍物的空间区域内，表现出用于局部探索的穿梭运行，并且可以通过趋化作用“逃脱”，再次说明了互补信号通路中所需的平衡。
