基于纳米机器人的细胞粘附力的定量研究
发布时间：2018-09-10 15:16
【摘要】：细胞粘附是一种对所有多细胞和单细胞生物都极其重要的基本现象,在组织生长、细胞间交流、细胞迁移、细胞新陈代谢、发炎和感染中起着重要的作用。对细胞粘附力的研究有助于揭示生命的奥秘,促使新的疾病诊断和治疗手段诞生,推动纳米生物力学的进一步发展,甚至为生物的基因改造提供信息。在众多的方法与技术中,原子力显微镜(Atomic Force Microscope,AFM)以其测力精度高、范围广且能在生理环境中检测等优势成为纳米生物力学中应用最广泛的研究手段之一。基于自主研发的纳米机器人,本文应用改进的AFM单细胞力谱法对哺乳动物细胞的粘附力进行定量研究。在保持AFM单细胞力谱法高精度的同时,采用中空探针吸附细胞,代替了传统探针的化学修饰,提高了细胞粘附力的测试效率,为细胞力学的研究提供了新的测试技术与方法。主要研究内容包括:首先,本文改进了传统的AFM单细胞力谱法,采用中空探针代替传统AFM探针。设计了中空探针气动装置,使中空探针内产生负压而吸附细胞,减少了固定细胞与标定探针所花的时间,提高了测试的效率。同时,该方法允许细胞和基底长时间的接触,扩大了粘附力的测量范围。接着,本文对中空探针负压提拉细胞的过程进行了模拟。基于薄膜-液体连续介质粘附模型提出并建立了贴壁细胞的力学模型,利用有限元法对不同内径的中空探针负压提拉细胞的过程进行了仿真,得到了探针内径大小对细胞形变与应力的影响。其次,本文分析了外力作用下粘附分子连接(Adhesion Molecular Bonds)的解离反应。基于液体中分子连接受力解离的布朗运动动理学理论,分析中空探针负压提拉细胞过程中粘附分子连接特性,得到了外力及其加载速率对粘附分子连接解离反应速率、寿命、强度的影响规律。最后,本文采用改进的AFM单细胞力谱法对细胞与基底的粘附力进行测量。测量结果精确、效率高、范围广。应用该方法可以得到细胞粘附力与探针上升速度关系以及细胞粘附力与时间的关系。基于纳米机器人系统,改进的AFM单细胞力谱法能够在液相中对细胞进行三维操作和粘附力测试,对纳米生物力学的研究具有推动效应,并为纳米科学的研究提供了新的途径。
[Abstract]:Cell adhesion is a basic phenomenon that is extremely important to all multicellular and single-celled organisms. It plays an important role in tissue growth, intercellular communication, cell migration, cell metabolism, inflammation and infection. The study of cell adhesion will help to reveal the mystery of life, promote the birth of new methods of disease diagnosis and treatment, promote the further development of nano-biomechanics, and even provide information for the genetic modification of organisms. Among the many methods and techniques, atomic force microscope (Atomic Force Microscope,AFM) has become one of the most widely used research methods in nano-biomechanics because of its advantages of high precision, wide range and can be detected in physiological environment. Based on the self-developed nanorobot, the adhesion of mammalian cells was quantitatively studied by modified AFM single cell force spectroscopy. While maintaining the high accuracy of AFM single cell force spectrum method, the hollow probe was used to adsorb the cells, instead of the chemical modification of the traditional probe, which improved the efficiency of the cell adhesion test, and provided a new testing technique and method for the study of cell mechanics. The main research contents are as follows: firstly, the traditional AFM single cell force spectrum method is improved and the hollow probe is used instead of the traditional AFM probe. A hollow probe pneumatic device was designed to produce negative pressure and adsorb the cells in the hollow probe, which reduced the time between the fixed cell and the calibrated probe, and improved the efficiency of the measurement. At the same time, the method allows long contact between the cell and the substrate, expanding the range of adhesion. Then, the process of hollow probe negative pressure pulling cells was simulated. Based on the membrane liquid continuum adhesion model, a mechanical model of adherent cells was proposed and established. The process of negative pressure Czochralski cells with different inner diameters was simulated by finite element method. The effects of probe diameter on cell deformation and stress were obtained. Secondly, the dissociation reaction of adhesion molecule attached to (Adhesion Molecular Bonds) under external force was analyzed. Based on the Brownian kinematics theory of molecular connection dissociation in liquid, the bonding characteristics of adhesion molecules in the process of negative pressure Czochralski cell with hollow probe are analyzed. The effect of external force and loading rate on the dissociation rate and lifetime of adhesion molecule is obtained. The influence law of strength. Finally, the adhesion between the cell and the substrate was measured by modified AFM single cell force spectroscopy. The measurement results are accurate, high efficiency and wide range. By using this method, the relationship between the cell adhesion force and the rising speed of the probe and the relationship between the cell adhesion force and the time can be obtained. Based on the nano-robot system, the improved AFM single-cell force spectrum method can perform three-dimensional operation and adhesion test of cells in liquid phase, which can promote the research of nano-biomechanics and provide a new way for the research of nanoscience.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：Q27;TP242
本文编号：2234824
[Abstract]:Cell adhesion is a basic phenomenon that is extremely important to all multicellular and single-celled organisms. It plays an important role in tissue growth, intercellular communication, cell migration, cell metabolism, inflammation and infection. The study of cell adhesion will help to reveal the mystery of life, promote the birth of new methods of disease diagnosis and treatment, promote the further development of nano-biomechanics, and even provide information for the genetic modification of organisms. Among the many methods and techniques, atomic force microscope (Atomic Force Microscope,AFM) has become one of the most widely used research methods in nano-biomechanics because of its advantages of high precision, wide range and can be detected in physiological environment. Based on the self-developed nanorobot, the adhesion of mammalian cells was quantitatively studied by modified AFM single cell force spectroscopy. While maintaining the high accuracy of AFM single cell force spectrum method, the hollow probe was used to adsorb the cells, instead of the chemical modification of the traditional probe, which improved the efficiency of the cell adhesion test, and provided a new testing technique and method for the study of cell mechanics. The main research contents are as follows: firstly, the traditional AFM single cell force spectrum method is improved and the hollow probe is used instead of the traditional AFM probe. A hollow probe pneumatic device was designed to produce negative pressure and adsorb the cells in the hollow probe, which reduced the time between the fixed cell and the calibrated probe, and improved the efficiency of the measurement. At the same time, the method allows long contact between the cell and the substrate, expanding the range of adhesion. Then, the process of hollow probe negative pressure pulling cells was simulated. Based on the membrane liquid continuum adhesion model, a mechanical model of adherent cells was proposed and established. The process of negative pressure Czochralski cells with different inner diameters was simulated by finite element method. The effects of probe diameter on cell deformation and stress were obtained. Secondly, the dissociation reaction of adhesion molecule attached to (Adhesion Molecular Bonds) under external force was analyzed. Based on the Brownian kinematics theory of molecular connection dissociation in liquid, the bonding characteristics of adhesion molecules in the process of negative pressure Czochralski cell with hollow probe are analyzed. The effect of external force and loading rate on the dissociation rate and lifetime of adhesion molecule is obtained. The influence law of strength. Finally, the adhesion between the cell and the substrate was measured by modified AFM single cell force spectroscopy. The measurement results are accurate, high efficiency and wide range. By using this method, the relationship between the cell adhesion force and the rising speed of the probe and the relationship between the cell adhesion force and the time can be obtained. Based on the nano-robot system, the improved AFM single-cell force spectrum method can perform three-dimensional operation and adhesion test of cells in liquid phase, which can promote the research of nano-biomechanics and provide a new way for the research of nanoscience.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：Q27;TP242
【参考文献】
相关博士学位论文 前1条
1 于淼;基于原子力显微镜的细胞若干力学特性的定量研究[D];哈尔滨工业大学;2015年
相关硕士学位论文 前4条
1 宋健民;基于AFM的细胞核力学特性原位测试的研究[D];哈尔滨工业大学;2015年
2 王浩;基于纳米镊子的细胞粘弹性测试方法研究[D];哈尔滨工业大学;2014年
3 尹穆楠;基于纳米机器人的生物活细胞力学特性表征[D];哈尔滨工业大学;2013年
4 吴爱文;AFM纳米镊子激光测力系统设计[D];哈尔滨工业大学;2011年
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