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题名: 基于原子力显微镜的细胞动态机械特性表征与分析研究
其他题名: Characterization and Analysis of Cell Dynamical Mechanics based on Atomic Force Microscopy
作者: 魏发南
导师: 李广勇 ; 刘连庆
关键词: 细胞生物力学 ; 原子力显微镜 ; 有限元仿真 ; 细胞核机械特性 ; 细胞机械特性的时间动态性
页码: 105页
学位专业: 机械电子工程
学位类别: 博士
答辩日期: 2015-11-26
授予单位: 中国科学院沈阳自动化研究所
学位授予地点: 中国科学院沈阳自动化研究所
作者部门: 机器人学研究室
中文摘要: 针对细胞生物力学研究存在的突出问题,本文在系统研究分析AFM表征细胞力学信息过程的基础上,开展了如下的研究工作。(1)细胞机械特性参数反馈校准方法:针对传统细胞力学参数估算的开环特点,本文提出了一种基于有限元仿真的反馈迭代参数校准方法。假定细胞为粘弹性材料,我们采用该校准方法从AFM表征结果分析得到了细胞的粘弹性参数;并进一步验证了所获取参数的可靠性。(2)细胞动态机械特性本质的判别研究:针对传统赫兹模型不能正确处理细胞机械特性本质的问题,考虑细胞表现出的明显动态力学特征,本文从理论分析,数值仿真以及实验验证三个层次分析比较了粘弹性和多孔弹性两种动态材料力学模型对描述细胞的适用性。结果表明,细胞的机械特性本质是多孔弹性,而非粘弹性。在多孔弹性假设下,本文进一步分析获取了不同细胞的多孔弹性参数。(3)细胞核动态机械特性的表征与分析:本文利用AFM表征了离体细胞核的机械特性。实验结果表明细胞核也存在明显的动态力学特征,并且其机械特性本质更接近于多孔弹性。本文分析估算了不同细胞细胞核的多孔弹性参数。(4)细胞动态机械特性的随细胞分裂过程的变化规律研究:针对传统细胞力学表征方法将细胞静态化处理的缺陷,本文利用AFM动态跟踪了活细胞在不同分裂阶段的机械特性。研究结果表明:不同生理阶段的细胞机械特性差异明显。处于分裂中期阶段的球形细胞表现为线弹性,而处于分裂间期以及分裂末期的细胞表现为多孔弹性。本文还对比了肿瘤细胞与正常细胞机械特性随时间变化的规律,发现肿瘤细胞在整个分裂周期中都表现出动态机械特性,且其机械特性本质是多孔弹性。通过相关研究工作,本文完善了细胞生物力学信息检测手段,深化了对细胞机械特性的认识,拓宽了生物力学的研究领域。
英文摘要: In order to tackling those issues, we thoroughly investigated the AFM probe-cell interaction system and performed the work listed as following. (1) Development of a feedback parameter strategy for cell mechanical property evaluation. In this paper, assuming cells to be viscoelastic, we proposed and realized the iterative correction method based on finite element simulation. Using the developed approach, the viscoelastic parameters for HEK-293 cells were estimated. And the reliability of the estimated parameters was demonstrated. (2) Cell mechanics nature determination. Since Hertz model is far from correct in dealing with cell mechanics. In this paper, we attempted to clarify the cell mechanics nature through theoretical analysis, numerical simulation and experiment demonstration. A comparison between viscoelasticity and poroelasticity suggested that cell is poroelastic, rather than viscoelastic. The poroelastic parameters of different cells were estimated and compared. (3) Characterization and evaluation of cell nucleus’s mechanics. In this paper, we studied the mechanical property of cell nuclei in vitro using AFM. Experiment results showed the dynamical mechanical property of cell nuclei. And the nature of cell nucleus’s mechanics was proved to be poroelastic. Subsequently, the poroelastic parameters of different cell nuclei were evaluated. (4) Investigation of the dynamics of the dynamical mechanics of living cells. We tracked the changes of cell mechanics as time evolves. The study concluded that the cell mechanics varies much at different stage of mitosis. To be specific, the cells at metaphase are round and linear elastic. While, the cells at interphase and telophase are poroelastic. Further investigation on cancer cells showed that cancer cells are poroelastic through all the cells'life. In sum, our work promotes the characterization and analysis method for cell mechanics estimation, deepen our understanding of cell mechanical property, and broaden the study field on biology mechanics.
语种: 中文
产权排序: 1
内容类型: 学位论文
URI标识: http://ir.sia.cn/handle/173321/17535
Appears in Collections:机器人学研究室_学位论文

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Recommended Citation:
魏发南. 基于原子力显微镜的细胞动态机械特性表征与分析研究[D]. 中国科学院沈阳自动化研究所. 中国科学院沈阳自动化研究所. 2015.
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