细胞在缓变刚度基质上趋硬性迁移的数值试验

Numerical Test for Cell Durotaxis Migration on Substrate with Moderate Gradient Stiffness

目的以成纤维细胞为模式细胞,光聚法制备的具有缓变刚度的水凝胶为基质,分析基质的工艺和性能参数对细胞迁移进程的影响,为有关人工基质的设计和制作提供理论指导。方法构建试验系统的数学模型,编制相应的计算机求解程序,包括细胞模型的黏弹性动力学有限元、细胞与基质间黏着斑的形成和解离动力学方程、动边界和时间多尺度问题的求解策略。结果给出基于实验数据的基质工艺参数与基质性能参数之间的关系式;当基质刚度一定时,速度和牵引力随基质刚度的增加而增大,并且伴有快速波动现象,随观察时间的延长,细胞运动状态将逐渐趋于稳定;适量增加基质刚度梯度将明显促进细胞迁移,而且细胞在较大刚度梯度的基质上能够保持一定的极限速度;光掩模不透明度梯度越小,基质刚度梯度越大,细胞到达指定位置耗时越少。试验结果与文献报道的有关实验结果相符。结论试验结果为测试光聚法制备的缓变刚度水凝胶基质的工艺参数和性能参数对细胞迁移进程的影响提供了一个有效的数字仿真平台。

Objective Based on fibroblast cell model and photopolymerized hydrogel substrate with moderate gradient stiffness, to analyze the effect of process and performance parameters on cell migration and provide theoretical guidance for artificial scaffold design and fabrication. Methods A mathematical model of the test system was built and the corresponding numerical program was compiled, including viscoelastic dynamic finite element of the cell model, reaction kinetic equation of focal adhesions, and the strategy to deal with dynamic boundary and multi-scale time. Results The relationship between process parameters and performance parameters was formulated based on experimental data;cell migration speed and traction increased with the substrate stiffness increasing and were accompanied by rapid fluctuation when stiffness gradient was constant, then cell movement gradually stabilized with the extension of observation time. Increasing stiffness gradient moderately obviously promoted cell migration, and cells could maintain a limited speed on substrate with a large stiffness gradient. Smaller photomask opacity gradient resulted in larger substrate stiffness gradient and less time spent for cell to reach the target. These results agreed with the experimental results reported in the literature. Conclusions The experimental result provided an effective digital simulation platform to test the influence of process and performance parameter of photopolymerized hydrogel substrate with moderate gradient stiffness on cell migration.