Li Yong-Jiang, Yu Miao, Xue Chun-Dong, Zhang Hai-Jun, Wang Guo-Zhen, Chen Xiao-Ming, Qin Kai-Rong
School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian 116024, China.
School of Biomedical Engineering, Dalian University of Technology, Dalian 116024, China.
Micromachines (Basel). 2021 Feb 7;12(2):161. doi: 10.3390/mi12020161.
Intracellular calcium dynamics play essential roles in the proper functioning of cellular activities. It is a well known important chemosensing and mechanosensing process regulated by the spatio-temporal microenvironment. Nevertheless, how spatio-temporal biochemical and biomechanical stimuli affect calcium dynamics is not fully understood and the underlying regulation mechanism remains missing. Herein, based on a developed microfluidic generator of biochemical and biomechanical signals, we theoretically analyzed the generation of spatio-temporal ATP and shear stress signals within the microfluidic platform and investigated the effect of spatial combination of ATP and shear stress stimuli on the intracellular calcium dynamics. The simulation results demonstrate the capacity and flexibility of the microfluidic system in generating spatio-temporal ATP and shear stress. Along the transverse direction of the microchannel, dynamic ATP signals of distinct amplitudes coupled with identical shear stress are created, which induce the spatio-temporal diversity in calcium responses. Interestingly, to the multiple combinations of stimuli, the intracellular calcium dynamics reveal two main modes: unimodal and oscillatory modes, showing significant dependence on the features of the spatio-temporal ATP and shear stress stimuli. The present study provides essential information for controlling calcium dynamics by regulating spatio-temporal biochemical and biomechanical stimuli, which shows the potential in directing cellular activities and understanding the occurrence and development of disease.
细胞内钙动力学在细胞活动的正常运作中发挥着重要作用。它是一个由时空微环境调节的众所周知的重要化学传感和机械传感过程。然而，时空生化和生物力学刺激如何影响钙动力学尚未完全了解，其潜在的调节机制仍然缺失。在此，基于开发的生化和生物力学信号微流控发生器，我们从理论上分析了微流控平台内时空ATP和剪切应力信号的产生，并研究了ATP和剪切应力刺激的空间组合对细胞内钙动力学的影响。模拟结果证明了微流控系统在产生时空ATP和剪切应力方面的能力和灵活性。沿着微通道的横向方向，产生了不同幅度的动态ATP信号与相同的剪切应力相结合，这诱导了钙反应的时空多样性。有趣的是，对于多种刺激组合，细胞内钙动力学呈现出两种主要模式：单峰模式和振荡模式，显示出对时空ATP和剪切应力刺激特征的显著依赖性。本研究为通过调节时空生化和生物力学刺激来控制钙动力学提供了重要信息，这显示了在指导细胞活动和理解疾病发生发展方面的潜力。
