兰州大学机构库 >土木工程与力学学院
癌细胞力学性质测量及放射诱导下细胞损伤的生物力学研究
Alternative TitleMechanical Property Measurement of Cancer Cells and Biomechanics of Cell Damage Induced by Irradiation
张宝平
Thesis Advisor王记增
2016-06-04
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keyword碳离子辐射 人肝癌细胞 细胞凋亡 形态学重构 力学性质 磷脂双分子层膜 细胞刚度 红细胞 生物型原子力显微镜
Abstract本文基于重离子辐射的诱导作用建立了体外细胞凋亡、体内细胞损伤模型。通过采用MTT、免疫印迹技术等分子生物学方法结合基于原子力显微镜的单细胞力学技术以及临床细胞学分析,研究如何将细胞力学特性的变化纳入到评估癌症杀伤机制、治疗效果以及副作用的研究体系当中。获得的创新性研究成果如下: (1) 基于力学性质变化表征癌细胞与正常细胞之间差异,发现肝癌细胞系较正常肝细胞弹性小(软),随着癌细胞侵袭力的增加,其细胞弹性值降低。且细胞粘附力和粘附能量也随着癌细胞侵袭力的增加,表现一致增加。 (2) 基于碳离子辐射对肝癌细胞杀伤的效果,通过对体外肝癌细胞凋亡模型中分子通路的分析,从力学特性表征的角度,发现凋亡过程中细胞力学性质、形态学重构与分子通路之间的紧密耦合相互作用而调控细胞凋亡的进程。针对细胞凋亡过程中体现出的典型形态学特征,应用统计热力学方法首次提出描述细胞凋亡过程的力学模型,揭示了凋亡小体出芽过程的力学机制。 (3) 针对辐照对金黄地鼠红细胞损伤副作用的评价,从力学性质与构型变化两方面阐明了离子辐射诱导红细胞损伤的生物力学机理。并首次提出红细胞刚度的变化可用于评价离子辐射引起红细胞损伤分级以及副作用的影响。
Other AbstractBased on the induction effect of cell apoptosis by heavy ion RT, this study established a canonical cell apoptosis model in vitro and cell damage model in vivo. By means of molecular biology methods, such as MTT assay, and western blotting technique and combining with single cell mechanics technique based on atomic force microscopy (AFM) and clinical cytology analysis, we investigate how the change of cell mechanical properties would be brought into to the research system to assess cancer killing mechanism, therapeutic effect and adverse effects of radiation. Obtained innovative research results as follows: (1) Based on the change of mechanical properties to characterize the differences between cancer cells and normal cells, we found that hepatocellular carcinoma cell (HCC) lines showed the smaller value of cell elasticity compared with normal hepatocyte (NH) line (more softer), with the increasing of the HCC invasiveness, which exhibited a lower cell elasticity value. Meawhile, cell adhesion force and surface adhesion energy increased with the enhancing of invasive potential in the HCCs. (2) Based on the cancer cell-killing effects by carbon ion irradiation, five HCCs and one NHs were treated with CII technique to establish a canonical cell apoptosis model by regualting the molecular pathways in vitro. From the perspective of the mechanical signatures to characterize, we found a close relationship during the apoptotic process that appears to exist among the cell microstructure, cell mechanical properties, actin cytoskeletal organization, and expression of apoptotic signaling molecules. These findings imply that the cell mechanical properties, morphological remodeling and molecular pathways are tightly coupled interaction to regulate the progression of apoptosis. Furthermore, based on the classical morphological features during the the onset of apoptosis, for the first time, we proposed a theoretical model of apoptosis which revealed that the characteristic change in cellular budding of apoptotic bodies was mainly dominated by the mechanical mechanism. (3) Based on the viewpoint of irradiation-induced damage-effect evaluation of erythrocytes in the Syrian hamsters, this clarify the biomechanical mechanism of ionizing radiation induction to erythrocytes damage from two aspects between mechanical properties and configuration changes. As well, we for the first time put forward the change of erythrocyte rigidity to evaluate the ionizing radiation damage ...
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/226731
Collection土木工程与力学学院
Recommended Citation
GB/T 7714
张宝平. 癌细胞力学性质测量及放射诱导下细胞损伤的生物力学研究[D]. 兰州. 兰州大学,2016.
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