State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, China; University of Chinese Academy of Sciences, Beijing, China.
State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang, China.
Biophys J. 2018 Jan 9;114(1):188-200. doi: 10.1016/j.bpj.2017.11.002.
Studies on the contractile dynamics of heart cells have attracted broad attention for the development of both heart disease therapies and cardiomyocyte-actuated micro-robotics. In this study, a linear dynamic model of a single cardiomyocyte cell was proposed at the subcellular scale to characterize the contractile behaviors of heart cells, with system parameters representing the mechanical properties of the subcellular components of living cardiomyocytes. The system parameters of the dynamic model were identified with the cellular beating pattern measured by a scanning ion conductance microscope. The experiments were implemented with cardiomyocytes in one control group and two experimental groups with the drugs cytochalasin-D or nocodazole, to identify the system parameters of the model based on scanning ion conductance microscope measurements, measurement of the cellular Young's modulus with atomic force microscopy indentation, measurement of cellular contraction forces using the micro-pillar technique, and immunofluorescence staining and imaging of the cytoskeleton. The proposed mathematical model was both indirectly and qualitatively verified by the variation in cytoskeleton, beating amplitude, and contractility of cardiomyocytes among the control and the experimental groups, as well as directly and quantitatively validated by the simulation and the significant consistency of 90.5% in the comparison between the ratios of the Young's modulus and the equivalent comprehensive cellular elasticities of cells in the experimental groups to those in the control group. Apart from mechanical properties (mass, elasticity, and viscosity) of subcellular structures, other properties of cardiomyocytes have also been studied, such as the properties of the relative action potential pattern and cellular beating frequency. This work has potential implications for research on cytobiology, drug screening, mechanisms of the heart, and cardiomyocyte-based bio-syncretic robotics.
关于心肌细胞收缩动力学的研究，因其对心脏病治疗和心肌细胞驱动的微机器人技术的发展都具有重要意义，而受到广泛关注。在本研究中，提出了一个亚细胞尺度的单个心肌细胞的线性动力学模型，用于描述心肌细胞的收缩行为，系统参数代表了活心肌细胞亚细胞成分的力学特性。利用扫描离子电导显微镜测量的细胞跳动模式来识别动态模型的系统参数。实验采用了一个对照组和两个实验组的心肌细胞，实验组分别用细胞松弛素-D 或诺考达唑处理，基于扫描离子电导显微镜测量、原子力显微镜压痕测量细胞杨氏模量、微柱技术测量细胞收缩力以及细胞骨架的免疫荧光染色和成像，来识别模型的系统参数。所提出的数学模型通过对照组和实验组之间的细胞骨架、跳动幅度和收缩性的变化进行了间接和定性验证，通过模拟和实验组与对照组细胞杨氏模量和等效综合细胞弹性比之间 90.5%的显著一致性进行了直接和定量验证。除了亚细胞结构的力学特性（质量、弹性和粘性）之外，还研究了心肌细胞的其他特性，如相对动作电位模式和细胞跳动频率的特性。这项工作对细胞生物学、药物筛选、心脏机制和基于心肌细胞的生物合成机器人技术的研究具有潜在意义。
