利用光镊研究生物细胞的力学行为
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摘要
生命科学是研究生命现象、生命活动的本质、特征和发展规律的自然科学,与人类生存、人民健康以及社会发展有着密切的关系,是当今全球范围内最受关注的基础自然科学。其中,细胞生物学是生命科学的基础学科之一,它是以细胞为研究对象,从细胞的整体水平、亚显微水平以及分子水平等三个层次,研究细胞和细胞器的结构和功能。活细胞的新陈代谢、跨膜转运、信号转导等生命活动,都是细胞与其他生物大分子(如蛋白质、多糖、核酸等)相互作用的结果,在这些相互作用过程中,细胞和大分子的力学行为会发生不同的变化,换句话说,细胞和大分子的力学行为变化可以反映其功能及活动规律。传统的细胞生物学和分子生物学研究,大都是基于生物化学或药理学实验中的一些分子浓度变化而做出的,是许多细胞或分子活动的一个平均结果,往往掩盖了各个分子的个性,因此特别需要从单细胞、单分子的层次上研究其活动规律。
生物学研究不但依赖物理、化学知识,同时还依靠后者提供的实验仪器和研究手段,例如蛋白质电泳仪、光学和电子显微镜、断层扫描仪等等。而在单细胞、单分子层次上进行细胞生物学研究,光镊是一项非常适合的技术。事实上,光镊自诞生起就和生物学紧密相连,由于其独特的技术特点,一直以来被生物学家所青睐。目前,光镊已成为细胞生物学和分子生物学研究中重要的工具。
光镊可以捕获和操控几十纳米到几十微米大小的粒子,它还可以作为微小力力的探针,测量皮牛亚皮牛量级的力,正好可以用来研究生物细胞的力学行为,以及细胞与生物大分子如蛋白质等的相互作用等,进而从单细胞层次上揭示细胞生命活动的基本规律。
在本文的工作中,将光镊技术应用于细胞生物学力学行为的研究领域,即利用实验室的光镊技术平台,进行细胞力学性质的测量研究,主要研究了免疫细胞对靶细胞的特异性识别,对细胞表面受体分子与抗体分子间的相互作用进行了测量,从理论和实验两个方面研究了渗透压对红细胞变形性质的影响,另外,为了更加方便的研究生物细胞的膜弹性行为,发展了新型的光镊技术。
免疫是人体的一种生理功能,人体依靠免疫细胞识别外来抗原,产生特异性免疫应答,来维持机体健康。NK细胞是免疫细胞的一种,自发现以来逐渐成为免疫学领域的一个热点。NK细胞活化过程的分子基础非常复杂,简单可以描述为效应细胞与靶细胞相互作用,效应细胞表面分子识别靶细胞上的配体,形成免疫突触,最终杀伤靶细胞。K562是NK92细胞的杀伤敏感细胞,然而对于这对细胞的识别和杀伤机制一直不清楚,我们利用光镊捕获NK细胞与靶细胞接触,实时观察NK细胞对靶细胞K562的杀伤作用,发现K562细胞发生形变,表面出现巨大囊泡,但细胞膜没有破裂。研究结果可能有助于揭示NK92对K562的杀伤机制。
免疫细胞的活化与其表面受体分子有紧密的关系。淋巴细胞功能相关抗原-1可能是NK细胞识别杀伤靶细胞的早期参与者,LFA-1是在CTL介导靶细胞杀伤实验中发现的,它与机体自身免疫疾病以及肿瘤复发等密切相关。我们利用光镊研究了NK细胞表面LAF-1的单分子行为,发现NK细胞与包被了LFA-1抗体的小球之间的结合力随二者接触时间的延长而增强,表明NK细胞表面LFA-1分子可能会受LFA-1抗体影响而发生局部聚集。我们的研究不仅提供了一种实时观察单细胞间相互作用的方法,还建立了研究单分子对细胞活动影响的研究方法,推测存在一种新的诱导LFA-1分子活化的信号传导模式。
人类的红细胞没有细胞核,有着相对简单的结构,同时具有轴对称的形状,经常作为细胞力学模型而被研究。红细胞的变形对血液流动有着重要的影响,与一些疾病也有着直接的关联。由于红细胞的变形受到周围环境如渗透压、pH值等因素的影响,因此我们利用光镊技术对不同渗透压下红细胞的形变特征进行了研究,发现等渗条件下双凹形的红细胞形变能力最强,渗透压降低时,红细胞形变能力下降,其主要是由于细胞形状的改变造成的,而在高渗条件下,细胞变形能力同样减弱,主要原因是细胞内液粘度呈指数增加。另外,我们还利用ABAQUS有限元软件对不同形状的红细胞变形进行了模拟,模拟结果与实验结果基本相符。
光镊研究细胞膜弹性常用的方法是利用小球做手柄来拉伸细胞,实际上,细胞被光阱捕获时形状会发生微小变化,如果细胞处于阱位不断变化的光阱中,其形变就会比较大而可以很容易的测量。根据这个思想,我们利用旋转玻片实现了分时复用多光阱,利用该分时复用多光阱研究了红细胞的变形特点,同时还实现了多粒子的捕获,并从理论和实验两方面研究了不同切换频率下的有效光阱刚度。
本实验室一直以来以光镊技术研究为主,在生物学应用中,一直采取物理学提供工具、生物学提供样品的合作方式,但由于受到样品条件的限制,很多研究未能继续深入下去就草草结束。因此我们建立了自己的生物细胞培养室,创造生物样品制备条件。目前已经可以成功的培养Hela细胞并进行相关实验。
本论文的创新点在于利用光镊技术在单细胞层次上研究生物细胞的力学行为,包括细胞膜的变形规律、免疫细胞的特异性识别机制以及细胞表面分子和抗体分子间的相互作用,研究结果可以为阐明细胞生命活动的基本规律提供帮助。另外,还发展了新的产生多光阱的方法,可以在细胞力学行为研究中得到应用。
Life science focuses on the phenomenon of life, the nature, characteristics and developmental rules of life activities. It has close relation to human existence, health, and development of society, and attracts most worldwide attentions in basic sciences. Cell biology, which aims to study the cells, is one of the basic topics in life sciences, and it researches on the structure and function of cell and organelle from the cellular, sub-micron and molecular level. The metabolism, trans-membrane transport and signaling of live cells are all the results of the interaction of cell and other macromolecules such as protein, polysaccharides, and nucleic acid. In these interactions, the mechanical property of cell and molecule may change, and this change reflects the function and rules of cell activities. Traditional cell biological and molecular biological researches, which are based on the variation of concentration of some molecules in biochemical and pharmacological experiments, are the average results of the activities of many cells and molecules. The traditional research cannot reveal the performance of a single molecule; therefore, study of activities of a single molecule in cellular and molecular level is of great importance.
Biology not only relies on physical and chemical rules, but also relies on the experimental apparatus and research methods, such as protein electrophoresis, optical microscopy, electron microscopy, section scanner etc. Optical tweezers is a proper technique in cell biological research in cellular and molecular level. Factually, since its invention, optical tweezers has played important roles in biology and because of its technical uniqueness. Optical tweezers has attracted wide attention from biologists. Recently, optical tweezers becomes an important tool in cell biological and molecular biological researches.
Optical tweezers is able to trap and manipulate particles ranging in tens of nanometers to tens of microns, and can be used as probes to detect the forces of protein interaction or cellular forces in the range of pico-Newton to subpico-Newton. Furthermore, results from optical tweezers can be used to reveal life activity in cellular level.
In this thesis, we expand the application of optical tweezers into the areas of cell biology. The detailed researches lie in the measurements of the mechanical property of cells, specific identification of immune cell to target cell, interaction of antigen and antibody, theoretical and experimental research on the influence of osmotic pressure to the formation of cell membrane, and developed novel optical tweezers’technique to further study the mechanical property of cell membrane.
Immune is a physiological function of human body, which sustains healthy by identifying foreign antigen and generating specific immunological response. Natural Killer cells (NK cells) are one kind of immunological cells. Since its discovery, it gradually becomes hot topic in immunology. The activation of NK cell is very complex, and a simple description may goes as follows surface molecule on effective cell identifies ligand on target cell, forming immune synapse, and finally kill target cell. K562 cell is the sensitive cell of NK92, but the mechanism of identification and kill of this pair of cells hasn’t clear. We utilize optical tweezers manipulate NK cell contact target cell, observing the kill effect of NK cell to target cell in real time. Experimental results show that K562 cell deforms with a vesicle on the surface, and the cell membrane hasn’t broken. Our results help to reveal the kill mechanism of NK92 to K562.
The activation of NK cells has close relation with the surface receptors. Lymphocyte function associated antigen-1 (CD11a/CD18, LFA-1) is a member of the integrin family of cell surface receptors. It is possible one of the early actors in process of the recognition and killing of NK cells. LFA-1 was found in the killing experiment mediated by the CTLs and was likely to be involved in some immunological diseases and tumour recurrence. To study the activation mode of LFA-1 on the NK cell surfuse, a platform based on optical tweezers was constructed to observe the molecular behavior of LFA-1. According to the results, the adhesion force between an NK cell and a polystyrene microsphere coated with anti-LFA-1 antibody was confirmed to be time-dependent. And the force was increased with the time of contact between the cell and sphere which indicated the LFA-1 on cell surface has clustered induced by anti-LFA-1 antibody. So, a new method is developed in our works to study the interaction between two cells in real time and to observe the single molecular behavior. Our results may provide a clue to explore the activation mechanism of LFA-1 on NK cells.
The human red blood cell has a relatively simple structure, and it does not contain a nucleus. Consequently, it has often been regarded as‘model system’in the study of single living cells. The formation of RBC greatly influences the flow of blood, and relates with some diseases. Naturally, the RBC is in a surroundings with many physical parameters such as osmotic pressure, pH etc. We adopt optical tweezers to study the formation characteristics of RBC under different osmotic pressure. The cell has large deformation ability under isotonic pressure; while the cell has low deformation ability under hypotonic environment because of change of cell shape; and the cell also has low deformation ability under hypertonic pressure due to the exponential increase of concentration of intracellular liquid. Additionally, a simulation adopting ABAQUS software to simulate the deformation of RBC with different shapes is conducted, and the results agree well with our experimental results.
Traditional method adopting optical tweezers to measure the elasticity of cell is to use micro bead handle to stretch cell. In fact, the form of cell suffers tiny changes under the trap. When a cell exposed in a jumping optical tweezers, this change may be larger that can be easily measured. We realized time-sharing multiple optical tweezers utilizing tilt rotating glass plate to further manipulate multiple particles and to study the formation characteristic of red blood cells. Meanwhile, we utilize this novel technique to investigate the effective stiffness under different trap switching frequencies both theoretically and experimentally
The main researches of our lab focus on the optical tweezers’technique. In biological applications, we adopt the means of providing instruments by physicist and sample prepared by biologists. In many of the applications, because of the limitation of sample preparation, many researches cannot go in deep. Therefore, we setup our own cell cultivation room to independently cultivate cells in our lab. Recently, we can cultivate Hela cells and perform relative experiments.
The highlights of this thesis lie in research of the mechanical property of biological cell in cellular level utilizing optical tweezers. The main results include formation of cell membrane, specific identification of immunological cells and interaction of antigen and antibody in cell membrane. Our results help us understand the basic rules of life activities of cells. Additionally, we developed novel methods to generate multiple optical tweezers, which will find applications in the researches of mechanics of cells.
生物学研究不但依赖物理、化学知识,同时还依靠后者提供的实验仪器和研究手段,例如蛋白质电泳仪、光学和电子显微镜、断层扫描仪等等。而在单细胞、单分子层次上进行细胞生物学研究,光镊是一项非常适合的技术。事实上,光镊自诞生起就和生物学紧密相连,由于其独特的技术特点,一直以来被生物学家所青睐。目前,光镊已成为细胞生物学和分子生物学研究中重要的工具。
光镊可以捕获和操控几十纳米到几十微米大小的粒子,它还可以作为微小力力的探针,测量皮牛亚皮牛量级的力,正好可以用来研究生物细胞的力学行为,以及细胞与生物大分子如蛋白质等的相互作用等,进而从单细胞层次上揭示细胞生命活动的基本规律。
在本文的工作中,将光镊技术应用于细胞生物学力学行为的研究领域,即利用实验室的光镊技术平台,进行细胞力学性质的测量研究,主要研究了免疫细胞对靶细胞的特异性识别,对细胞表面受体分子与抗体分子间的相互作用进行了测量,从理论和实验两个方面研究了渗透压对红细胞变形性质的影响,另外,为了更加方便的研究生物细胞的膜弹性行为,发展了新型的光镊技术。
免疫是人体的一种生理功能,人体依靠免疫细胞识别外来抗原,产生特异性免疫应答,来维持机体健康。NK细胞是免疫细胞的一种,自发现以来逐渐成为免疫学领域的一个热点。NK细胞活化过程的分子基础非常复杂,简单可以描述为效应细胞与靶细胞相互作用,效应细胞表面分子识别靶细胞上的配体,形成免疫突触,最终杀伤靶细胞。K562是NK92细胞的杀伤敏感细胞,然而对于这对细胞的识别和杀伤机制一直不清楚,我们利用光镊捕获NK细胞与靶细胞接触,实时观察NK细胞对靶细胞K562的杀伤作用,发现K562细胞发生形变,表面出现巨大囊泡,但细胞膜没有破裂。研究结果可能有助于揭示NK92对K562的杀伤机制。
免疫细胞的活化与其表面受体分子有紧密的关系。淋巴细胞功能相关抗原-1可能是NK细胞识别杀伤靶细胞的早期参与者,LFA-1是在CTL介导靶细胞杀伤实验中发现的,它与机体自身免疫疾病以及肿瘤复发等密切相关。我们利用光镊研究了NK细胞表面LAF-1的单分子行为,发现NK细胞与包被了LFA-1抗体的小球之间的结合力随二者接触时间的延长而增强,表明NK细胞表面LFA-1分子可能会受LFA-1抗体影响而发生局部聚集。我们的研究不仅提供了一种实时观察单细胞间相互作用的方法,还建立了研究单分子对细胞活动影响的研究方法,推测存在一种新的诱导LFA-1分子活化的信号传导模式。
人类的红细胞没有细胞核,有着相对简单的结构,同时具有轴对称的形状,经常作为细胞力学模型而被研究。红细胞的变形对血液流动有着重要的影响,与一些疾病也有着直接的关联。由于红细胞的变形受到周围环境如渗透压、pH值等因素的影响,因此我们利用光镊技术对不同渗透压下红细胞的形变特征进行了研究,发现等渗条件下双凹形的红细胞形变能力最强,渗透压降低时,红细胞形变能力下降,其主要是由于细胞形状的改变造成的,而在高渗条件下,细胞变形能力同样减弱,主要原因是细胞内液粘度呈指数增加。另外,我们还利用ABAQUS有限元软件对不同形状的红细胞变形进行了模拟,模拟结果与实验结果基本相符。
光镊研究细胞膜弹性常用的方法是利用小球做手柄来拉伸细胞,实际上,细胞被光阱捕获时形状会发生微小变化,如果细胞处于阱位不断变化的光阱中,其形变就会比较大而可以很容易的测量。根据这个思想,我们利用旋转玻片实现了分时复用多光阱,利用该分时复用多光阱研究了红细胞的变形特点,同时还实现了多粒子的捕获,并从理论和实验两方面研究了不同切换频率下的有效光阱刚度。
本实验室一直以来以光镊技术研究为主,在生物学应用中,一直采取物理学提供工具、生物学提供样品的合作方式,但由于受到样品条件的限制,很多研究未能继续深入下去就草草结束。因此我们建立了自己的生物细胞培养室,创造生物样品制备条件。目前已经可以成功的培养Hela细胞并进行相关实验。
本论文的创新点在于利用光镊技术在单细胞层次上研究生物细胞的力学行为,包括细胞膜的变形规律、免疫细胞的特异性识别机制以及细胞表面分子和抗体分子间的相互作用,研究结果可以为阐明细胞生命活动的基本规律提供帮助。另外,还发展了新的产生多光阱的方法,可以在细胞力学行为研究中得到应用。
Life science focuses on the phenomenon of life, the nature, characteristics and developmental rules of life activities. It has close relation to human existence, health, and development of society, and attracts most worldwide attentions in basic sciences. Cell biology, which aims to study the cells, is one of the basic topics in life sciences, and it researches on the structure and function of cell and organelle from the cellular, sub-micron and molecular level. The metabolism, trans-membrane transport and signaling of live cells are all the results of the interaction of cell and other macromolecules such as protein, polysaccharides, and nucleic acid. In these interactions, the mechanical property of cell and molecule may change, and this change reflects the function and rules of cell activities. Traditional cell biological and molecular biological researches, which are based on the variation of concentration of some molecules in biochemical and pharmacological experiments, are the average results of the activities of many cells and molecules. The traditional research cannot reveal the performance of a single molecule; therefore, study of activities of a single molecule in cellular and molecular level is of great importance.
Biology not only relies on physical and chemical rules, but also relies on the experimental apparatus and research methods, such as protein electrophoresis, optical microscopy, electron microscopy, section scanner etc. Optical tweezers is a proper technique in cell biological research in cellular and molecular level. Factually, since its invention, optical tweezers has played important roles in biology and because of its technical uniqueness. Optical tweezers has attracted wide attention from biologists. Recently, optical tweezers becomes an important tool in cell biological and molecular biological researches.
Optical tweezers is able to trap and manipulate particles ranging in tens of nanometers to tens of microns, and can be used as probes to detect the forces of protein interaction or cellular forces in the range of pico-Newton to subpico-Newton. Furthermore, results from optical tweezers can be used to reveal life activity in cellular level.
In this thesis, we expand the application of optical tweezers into the areas of cell biology. The detailed researches lie in the measurements of the mechanical property of cells, specific identification of immune cell to target cell, interaction of antigen and antibody, theoretical and experimental research on the influence of osmotic pressure to the formation of cell membrane, and developed novel optical tweezers’technique to further study the mechanical property of cell membrane.
Immune is a physiological function of human body, which sustains healthy by identifying foreign antigen and generating specific immunological response. Natural Killer cells (NK cells) are one kind of immunological cells. Since its discovery, it gradually becomes hot topic in immunology. The activation of NK cell is very complex, and a simple description may goes as follows surface molecule on effective cell identifies ligand on target cell, forming immune synapse, and finally kill target cell. K562 cell is the sensitive cell of NK92, but the mechanism of identification and kill of this pair of cells hasn’t clear. We utilize optical tweezers manipulate NK cell contact target cell, observing the kill effect of NK cell to target cell in real time. Experimental results show that K562 cell deforms with a vesicle on the surface, and the cell membrane hasn’t broken. Our results help to reveal the kill mechanism of NK92 to K562.
The activation of NK cells has close relation with the surface receptors. Lymphocyte function associated antigen-1 (CD11a/CD18, LFA-1) is a member of the integrin family of cell surface receptors. It is possible one of the early actors in process of the recognition and killing of NK cells. LFA-1 was found in the killing experiment mediated by the CTLs and was likely to be involved in some immunological diseases and tumour recurrence. To study the activation mode of LFA-1 on the NK cell surfuse, a platform based on optical tweezers was constructed to observe the molecular behavior of LFA-1. According to the results, the adhesion force between an NK cell and a polystyrene microsphere coated with anti-LFA-1 antibody was confirmed to be time-dependent. And the force was increased with the time of contact between the cell and sphere which indicated the LFA-1 on cell surface has clustered induced by anti-LFA-1 antibody. So, a new method is developed in our works to study the interaction between two cells in real time and to observe the single molecular behavior. Our results may provide a clue to explore the activation mechanism of LFA-1 on NK cells.
The human red blood cell has a relatively simple structure, and it does not contain a nucleus. Consequently, it has often been regarded as‘model system’in the study of single living cells. The formation of RBC greatly influences the flow of blood, and relates with some diseases. Naturally, the RBC is in a surroundings with many physical parameters such as osmotic pressure, pH etc. We adopt optical tweezers to study the formation characteristics of RBC under different osmotic pressure. The cell has large deformation ability under isotonic pressure; while the cell has low deformation ability under hypotonic environment because of change of cell shape; and the cell also has low deformation ability under hypertonic pressure due to the exponential increase of concentration of intracellular liquid. Additionally, a simulation adopting ABAQUS software to simulate the deformation of RBC with different shapes is conducted, and the results agree well with our experimental results.
Traditional method adopting optical tweezers to measure the elasticity of cell is to use micro bead handle to stretch cell. In fact, the form of cell suffers tiny changes under the trap. When a cell exposed in a jumping optical tweezers, this change may be larger that can be easily measured. We realized time-sharing multiple optical tweezers utilizing tilt rotating glass plate to further manipulate multiple particles and to study the formation characteristic of red blood cells. Meanwhile, we utilize this novel technique to investigate the effective stiffness under different trap switching frequencies both theoretically and experimentally
The main researches of our lab focus on the optical tweezers’technique. In biological applications, we adopt the means of providing instruments by physicist and sample prepared by biologists. In many of the applications, because of the limitation of sample preparation, many researches cannot go in deep. Therefore, we setup our own cell cultivation room to independently cultivate cells in our lab. Recently, we can cultivate Hela cells and perform relative experiments.
The highlights of this thesis lie in research of the mechanical property of biological cell in cellular level utilizing optical tweezers. The main results include formation of cell membrane, specific identification of immunological cells and interaction of antigen and antibody in cell membrane. Our results help us understand the basic rules of life activities of cells. Additionally, we developed novel methods to generate multiple optical tweezers, which will find applications in the researches of mechanics of cells.
引文
1. Lindsay S M et.al. Potentiostatic deposition of DNA for scanning probe microscopy. Biophysical J, 1992, 61:1570-1584.
2. Florin, et.al. Adhesion forces between individual and receptor pairs. Science, 1994, 264:415-418.
3. Rief M. et.al. Reversible unfolding of individual titin immunoglobulin domains by AFM. Science, 1997, 276:1109-1112.s
4.李银妹,《光镊原理、技术和应用》,中国科学技术大学出版社,1996。
5. A. Ashkin, J.M. Dziedzic,J.E.Bjorkholm,S.Chu. Observation of a single-beam gradient force optical trap for dielectric particle,Opt.Lett.,1986,11:288.
6. A. Ashkin. History of optical trapping and manipulation of small-neutral particle, atoms, and molecules. IEEE J.Sel.Top. Quantum Elec., 2000, 6:841-856.
7. Yoshiharu Ishii, Toshio Yanagida, Single Molecule Detection in Life Science. Single Molecule, 2000, 1:s5-s16.
8. K. Kitamura, M. Tokunaga, A. H. Iwane, A Single Myosin Head Moves Along an Actin Filament with Regular Steps of 5.3 Nanometers. Nature, 1999, 397:129.
9. K. Visscher, M. J. Schnitzer, S. M. Block, Single Kinesin Molecules Studied with a Molecular Force Clamp. Nature, 1999, 400:184.
10. Y. Okada, N. Hirokawa, a Processive Single-Headed Motor: Kinesin Superfamily Protein KIF1A. Science, 1999, 283:1152.
11. Miklos S. Z. Kellermayer, Steven B. Smith, Carlos Bustamante, Mechaniccal Fatigue in repetitively Stretched Single Molecules of Titin. Biophysical Journal, 2001, 80:852-863.
12. Yu-Long Sun, Zong-Ping Luo, Kai-Nan An, Stretching Short Biopolymers Using Optical Tweezers. Biochemical and Biophysical Research Communications, 2001, 286:826-830.
13. Tadashi Fujii, Yu-Long Sun, Kai-Nan An, Mechanical Properties of Single Hyaluronan Molecules. Journal of Biomechanics, 2002, 35:527-531.
14. G. V. Shivashankar, G. Stolovitzky, A. Libchaber, Backscattering from a Techered Bead as a Probe of DNA Flexibility. Applied Physics Letters, 1998, 73:291-293.
15. Lebedev, P.N., Experimental examination of light pressure. Ann. Der Physik 6, 433.
16. Nichols, E.F., and Hull, G.F., Phys. Rev. 1901, 13:301.
17. J.E. Bjorkholm, R.R. Freeman, D.B. Pearson. Efficient transverse deflection of neutral atomic beams using spontaneous resonance-radiation pressure, Phys.Rev.A, 1981, 23:491.
18. W.D. Phllips, H.J. Metcalf. Laser cooling and electromagnetic trapping of neutral atoms., J.Opt.Soc.Am,B, 1985, 2:1751
19. A. Aspect, J. Dalibard, A. Heidmann,et al. Cooling atoms with stimulated emission., Phys.Rev.Lett., 1986, 57:1688.
20. David G. Grier, A revolution in optical manipulation. Nature, 2003, 424:810.
21. A. Ashkin, Acceleration and trapping of particles by radiation pressure, Phys.Rev.Lett., 1970, 24:156-159.
22. A. Ashkin and J.M.Dziedzic, Optical levitation of liquid drops by radiation pressure, Science, 1975, 187:1073-1075.
23. Ashkin, A. & Dziedzic, J. M., Optical levitation in high-vacuum. Appl. Phys. Lett. , 1976, 28:333–335.
24. Ashkin, A. & Dziedzic, J. M. Feedback stabilization of optically levitated particles. Appl.Phys. Lett. 1977, 30: 202–204
25. A. Ashkin, Observation of Light Scattering from Nanospherical Particles Using Optical Levitation, Appl. Optics, 1980, 19: 660.
26. Haowei Wang, Xiaohui Liu, Yinmei Li. Isolation of a single rice chromosome by optical micromanipulation. J.Opt. A: Pure Appl. Opt, 2004, 6:89.
27.王浩威,刘晓辉,李银妹等,应用光学微操作技术分选单条水稻染色体。生物物理学报,2004,20:50.
28. K. Visscher, M. J. Schnitzer, S. M. Block, Single Kinesin Molecules Studied with a Molecular Force Clamp. Nature, 1999, 400:184.
29. K. Svoboda, C. F. Schmidt, S. M. Block, Direct Observation of Kinesin Stepping by Optical Trapping Interferometry. Nature, 1993, 365:721-727
30. Mark J. Schnitzer, Steven, M. Block, Kinesin Hydrolyses one ATP per 8-nm Step. Nature, 1997, 388:386
31. Mark J. Schnitzer, Koen Visscher, Steven, M. Block, Force Production by Single KinesinMotors. Nature Cell Biology, 2000, 2:718.
32. Miklos S. Z. Kellermayer, Steven B. Smith, Henk L. Granzier, Folding-Unfolding Transitions in Single Titin Molecules Characterized with Laser Tweezers. Science, 1997, 276:1112-1116
33. Miklos S. Z. Kellermayer, Steven B. Smith, Carlos Bustamante, Mechaniccal Fatigue in repetitively Stretched Single Molecules of Titin. Biophysical Journal, 2001, 80:852-863.
34. Xiaohui Zhang, Kenneth Halvorsen, Timothy A. Springer et.al. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand Factor, Science, 2009, 324:1330-1334.
1. Trinchieri , G. Adv. Immunol. 1989 47:187–376.
2.金伯泉.细胞与分子免疫学[M].世界图书出版公司,1995:259-274
3. Gμmperz , J.E., and P. Parham. Nature. 1995 378: 245-248.
4. Ryan, J.C., E.C. Niemi el. J. Exp. Med. 1995 181:1911–1915.
5. Lanier, L.L. Curr. Opin. Immunol. 1997 9:126–131.
6. Yokoyama, W.M. Curr. Opin. Immunol.1998 10:298–305.
7. Marcenaro E et al, Eur J Immunol, 2003,33(12):3367-3376
8. Natarajan K, Dimasi N, Wang J,et al. Annu Rev Immunol, 2002,20,853
9. Moretta L, Bottino C, Pende D, et al. Eur J Immunol, 2002,32:1025
10.田志刚,魏海明等.中国免疫学杂志2004 20:33-35
11. Niwa R, Sakurada M, Kobayashi Y etal. Clin Cancer Res, 2005, 11(6): 2327-2336
12. Smyth M J, Cretney E, Kelly J M etal. Mol Immunol, 2005, 42:501-510.
13. Zompi S, Colucci F. Immunology Letters, 2005, 97:31-39.
14. Agerberth B, Charo J, Werr K etal. Blood, 2000, 96: 3086-3093.
15. Aurelie Wiedemann, Davie Depoil. 2006. Proc. Natl. Acad. Sci. USA. 103: 10985-10990.
16. Paul A.Negulescu el. Immunity, 1996 Vol. 4, 421-430.
17. Mikael Eriksson el.,Journal of Experimental Medicine 1999 7:1005-1012s
1. Lo CG, Lu TT, Cyster JG. Integrin-dependence of Iymphocyte entry into the splenic white pulp[J]. J Exp Med, 2003, 197:353-361.
2. Riaz AA, Wan MX, Schaefer T, et al. Fundamental and distinctroles of P-selectin and LFA-1 in ischemia/ reperfusion-induced leukocyte- endothelium interactions in the mouse colon[J]. Ann Surg, 2002, 236:777-784.
3. Melero, I., M.A. Balboa, J.L. Alonso, et al. Signaling through the LFA-1 leucocyte integrin actively regulates intercellular adhesion and tumor necrosis factor-alpha production in natural killer cells. European Journal of Immunology. 1993, 23(8): 1859-1865.
4. Sugie, K., Y. Minami, T. Kawakami, et al. Stimulation of NK-like YT cells via leukocyte function-associated antigen (LFA)-1. Possible involvement of LFA-1-associated tyrosine kinase in signal transduction after recognition of NK target cells. Journal of Immunology. 1995, 154(4): 1691-1698.
5. Luo, D., D. Vermijlen, K. Vanderkerken, et al. Involvement of LFA-1 in hepatic NK cell (pit cell)-mediated cytolysis and apoptosis of colon carcinoma cells. Journal of hepatology. 1999, 31(1): 110-116
6. Matsumoto, G., Y. Omi, U. Lee, et al. Adhesion mediated by LFA-1 is required for efficient IL-12-induced NK and NKT cell cytotoxicity. European Journal of Immunology. 2000, 30(12): 3723-3731
7. Borthwick NJ, Akbar AA, Buckley C, et al. Transendothelial migration a survival advantage to activated T lymphocytes: role of LFA-1/ICAM-1 interactions[J]j. Clin Exp Immunol, 2003, 134:246-252.
8. Richardson BC. Role of DNA methylation in the regulation of cell function: autoimmunity, aging and cancer[J]. J Nutr, 2002, 132:2401S-2405S.
9. Bangs Laboratoried, Inc. Covalent coupling, TechNote, 2002, 205:1-8.
10. H.T. Chen, Y.M.Li, L.R.Lou, et al. Single molecules detection in optical tweezers. Xing Zhu. Nano-Optics and Nano-Structures, Proceedings of SPIE Vol. 4923, 98-105.
11. Robert M.Simmons, J.T.Finer, S.Chu etc.“Quantitative Measurements of Force andDisplacement Using an Optical Trap,”J.Biophysical Journal, 1996, 70,1813-1822
12. Karl Otto Greulich. Micromanipulation by light in biology and medicine: the laser microbeam and optical tweezers.Berlin:Birkhauser Verlag, 1999, 90-96.
13. Florin E.-L., Pralle A., Stelzer E.H.K., et al.“Photonic force microscope calibration by thermal noise analysis,”J. Appl. Phys. A, 1998, 66, S75-S78 .
14.龚錾,陈洪涛,李银妹,四种光阱刚度测量法的实验研究与比较。中国科大学报,2005, 35:601。
1.易仁亮,邹霞英.红细胞变形性的影响因素[J].中国病理生理杂志,1995,11(6):658-659
2.范家骏,赵国欣.血液流变学基础与临床[M].陕西科学技术出版社,1995,1.
3.刘凝慧,祁友键21种不同纲脊椎动物红细胞变形能力的测量[J].徐州医学院学报,1989,9(3),181-185
4.尹翠娥.红细胞变形性的研究进展.重庆医学,1997,26(2):81-83
5.王红勇,何作云,李希楷冠心病患者红细胞变形性和全血粘弹性的变化.中华老年医学杂志,2001,20(6):455-456
6.何作云,王瑞兴.临床细胞流变学[M].重庆大学出版社,1997
7. Bessis M, Mohandas N A, Claude Feo. Automated ektacytometry: a new method of measuring red cell deformability and red cell indices. Blood Cell, 1980, 6:315-327
8. Fieger R , Grebe R. Cell-elastometry: a new method to measure erythrocyte elasticity. Biorheology , 1997 , 34 (3) : 223-291
9. Wen Zongyao , Yan Zonggyi , Gao Tie , et al. The study of effects of WGA and ConA on RBC receptors with a new Ektacytometry. Clinical and Microcirculation , 1997 ,17(6) :467～478
10.文宗曜,严宗毅,施岩等.测量红细胞膜剪切弹性模量及粘度的新方法,清华大学出版社,1997 ,741-744.
11.严宗毅.测量红细胞变形性的新方法[J].国外医学生物医学工程分册,1997,20(5):257-263
12.王玉英,王益民,史红.激光衍射法测量红细胞变形原理及有关问题分析[J].天津中医学院学报,2003,22(2):66-67
13. Shin S, Ku Y. Disposable laser-diffraction ektacytometry to measure red blood cell deformability[J]. Progress in Biomedical Optics and Imaging-Proceedings of SPIE, 2005, 5630(1): 168-176
14. Magus I. Gregersen, Cyrus A. Bryant, Walter E. Hammerle, Shunichi Usami and Shu Chien. Flow characteristics of human erythrocytes through polycarbonate sieves. Science,1967, 157(3790):825-827
15.王怡实用临床血液流变学,学苑出版社,1994,113-115
16. Micthison JM, Swann MM. The mechinical properties of the red cell surface[J]. J Exp Biol, 1954, 31:443-460
17. Lacelle PL. Effect of sphering on erythrocyte deformability. Biorheology. 1972, 9(2):51-59
18. Rand RP, Burton AC. Mechinical properties of red cell membrane[J]. Biophys J, 1964,4:115-135
19. Evans E.A., 1973. New membrane concept applied to the analysis of fluid shear-and micropipette-deformed red blood cells. Biophys. J. 13(9), 941-954.
20. Evans E.A., Waugh R. 1977. Osmotic correction to elastic area compressibility measurements on red cellmembrane. Biophys. J. 20:307
21. Ashkin A. Optical trapping and manipulation of single cells using infrared laser beams. Nature, 1987, 330:769-771
22. Svoboda K. Biological applications of optical forces. Annu Rev Biophys Biomol Struct, 1994, 23:247-285
23. Sheetz MP. Laser tweezers in cell biology. London, UK: Academic Press; 1998
24. Sylvie He′non, Guillanme Lenormand, Alain Richert and Francois Gallet. A new determination of shear modulus of the human erythrocyte membrane using optical tweezers. 1999, 76:1145-1151
25.周辉,李先锋,李银妹等.单光镊技术测量红细胞膜弹性新方法的建立.生物化学与生物物理进展,2001,28(6):904-907
26. Guillaume Lenormand. Direct measurement of the area expansion and shear module of the human red cell membrane skeleton. Biophysical Journal. 1999, 81:43-56
27. John Sleep, David Wilson, Robert Simmons, and Walter Gratzer. Elasticty of the red cell membrane and its relation to Hemolytic disorders: An optical tweezers study. Biophysical Journal. 1999, 77:3085-3095.
1. Ren Hongliang, Zhuang Lihui, Li Yinmei. Measurement of interaction potential between colloidal particles using dual optical tweezers. Chinese J. Lasers, 2008, 35(1):151-155
2. Furst EM. Applications of laser tweezers in complex fluid rheology[J]. Current Opinion in Colloid & Interface Science. 2005, 10: 79-86.
3. Dame RT, Noom MC, Wuite GJL. Bacterial chromatin organization by H-NS protein unravelled using dual DNA manipulation[J]. Nature. 2006, 444(16): 387-340.
4. Finer JT, Simmons RM, Spudich JA. Single myosin molecule mechanics: piconewton forces and nanometre steps[J]. Nature. 1994, 368: 113-119.
5. Guan Bo Liao, Paul B. Bareil, Arthur Chiou. et al. One-dimensional jumping optical tweezers for optical stretching of bi-concave human red blood cells. Optical Society of America. 2008, 16(3): 1996-2004.
6.陈洪涛.纳米光镊技术研究,2003,中国科学技术大学博士学位论文。
7. J.P.Pantina and E.M.Furst,“Directed assembly and rupture mechanics of colloidal aggregates,”Langmuir 20, 3940-3946 (2004).
8. Dufresne E.R., Grier D.G.. Optical tweezers and optical substrates created with diffractive optics.[J]. Rev. Sci. Instr., 1998, 69(5): 1974-1977.
9. Jesacher A., Furhapter S., Bernet S. et al. Diffractive optical tweezers in the Fresnel regime [J]. Opt. Exp., 2004, 12(10): 2243-2250.
10. Grier D.G.. A revolution in optical manipulation[J]. Nature, 2003, 424(6950): 810-816.
11. Grier D.G.. Roichma Y.. Holographic optical trapping[J]. Appl. Opt., 2006, 45(5): 880-887.
12. Roichman Y., Sun B. et al.. Optical forces arising from phase gradients[J]. Phys. Rev. Lett., 2008, 100(1): 013602.
13. Curtis JE, Koss BA, Grier DG. Dynamic holographic optical tweezers[J]. Opt. Commun. 2002, 207: 169-175.
14. Jesacher A, Maurer C, Fürhapter S et al. Optical tweezers of programmable shape with transverse scattering forces[J]. Opt. Commun. 2008, (281): 2207-2212.
15.任煜轩,周金华,吴建光等.全息光镊-光镊家族中极具活力的成员[J].激光与光电子学进展. 2008, 45(11): 35-41.
16.庄礼辉,任洪亮,李银妹等。同步斩波法测量胶体粒子间相互作用势,应用激光,2007,27:132-135.
17. J.P.Pantina and E.M.Furst,“Elasticity and critical bending moment of model colloidal aggregates,”Phys.Rev.Lett. 94, 138301 (2005).
18. Pleguezuelos E., Carnicer A., Andilla J. et.al.. Holotrap: Interactive hologram design for multiple dynamic optical trapping[J]. Computer Phys. Comm., 2007, 176:701-709.
19. Curtis J.E., Koss B.A., Grier D.G.. Dynamic holographic optical tweezers[J]. Opt. Comm., 2002, 207: 169-175.
20. Jesacher A., Maurer C., Furhapter S. et al.. Optical tweezers of programmable shape with transverse scattering forces[J]. Opt. Comm., 2008, 281: 2207-2212.
21. BingHuan Meng, JinHua Zhou, JianGuang Wu. et al. Inprovement of transverse trapping efficiency of optical tweezers[J]. Chin. Phys. Lett. 2008, 25(6): 2300-2302.
22.李银妹,楼立人,姚媛等.光阱阱位的观察与调节[J].中国激光Chinese Journal of Lasers. 1998, 25(12): 1083-1086.
23. Shenhua Xu, Yinmei Li, Liren Lou etc., Computer simulation of the collision frequency of two particles in optical tweezers. Chinese Physics, 2005, 14:382.
24. Zan Gong, Hongtao Chen, Shenghua Xu, Yinmei Li, Liren Lou. Monte-Carlo simulation of optical trap stiffness measurement. Optics Communications, 263(2), 229-234, 2006.
25.汪志诚.热力学与统计物理[M],北京:高等教育出版社,1980(2001年重印),P386.
1.司徒镇强,吴军正.细胞培养[M],世界图书出版公司,2007.
2.牟章兵,杜之渝,晏丕松.汉防己甲素等5种抗纤维化药物对离体HELA的抑制作用[J].眼科新进展,2006,26(8):592-596.
3. Grad JM, Bahlis NJ, Reis I, etal. Ascorbic acid enhances As2O3-induced cytotoxicity in multiple myeloma cells[J]. Blood, 2001,98(3): 805-813.
4.李新宇,李贵刚,朱雪菲.Bcl2xl/Lipofectamine2000比值对人HELA转染效率的影响[J].眼科新进展,2006,27(7):524-526.
2. Florin, et.al. Adhesion forces between individual and receptor pairs. Science, 1994, 264:415-418.
3. Rief M. et.al. Reversible unfolding of individual titin immunoglobulin domains by AFM. Science, 1997, 276:1109-1112.s
4.李银妹,《光镊原理、技术和应用》,中国科学技术大学出版社,1996。
5. A. Ashkin, J.M. Dziedzic,J.E.Bjorkholm,S.Chu. Observation of a single-beam gradient force optical trap for dielectric particle,Opt.Lett.,1986,11:288.
6. A. Ashkin. History of optical trapping and manipulation of small-neutral particle, atoms, and molecules. IEEE J.Sel.Top. Quantum Elec., 2000, 6:841-856.
7. Yoshiharu Ishii, Toshio Yanagida, Single Molecule Detection in Life Science. Single Molecule, 2000, 1:s5-s16.
8. K. Kitamura, M. Tokunaga, A. H. Iwane, A Single Myosin Head Moves Along an Actin Filament with Regular Steps of 5.3 Nanometers. Nature, 1999, 397:129.
9. K. Visscher, M. J. Schnitzer, S. M. Block, Single Kinesin Molecules Studied with a Molecular Force Clamp. Nature, 1999, 400:184.
10. Y. Okada, N. Hirokawa, a Processive Single-Headed Motor: Kinesin Superfamily Protein KIF1A. Science, 1999, 283:1152.
11. Miklos S. Z. Kellermayer, Steven B. Smith, Carlos Bustamante, Mechaniccal Fatigue in repetitively Stretched Single Molecules of Titin. Biophysical Journal, 2001, 80:852-863.
12. Yu-Long Sun, Zong-Ping Luo, Kai-Nan An, Stretching Short Biopolymers Using Optical Tweezers. Biochemical and Biophysical Research Communications, 2001, 286:826-830.
13. Tadashi Fujii, Yu-Long Sun, Kai-Nan An, Mechanical Properties of Single Hyaluronan Molecules. Journal of Biomechanics, 2002, 35:527-531.
14. G. V. Shivashankar, G. Stolovitzky, A. Libchaber, Backscattering from a Techered Bead as a Probe of DNA Flexibility. Applied Physics Letters, 1998, 73:291-293.
15. Lebedev, P.N., Experimental examination of light pressure. Ann. Der Physik 6, 433.
16. Nichols, E.F., and Hull, G.F., Phys. Rev. 1901, 13:301.
17. J.E. Bjorkholm, R.R. Freeman, D.B. Pearson. Efficient transverse deflection of neutral atomic beams using spontaneous resonance-radiation pressure, Phys.Rev.A, 1981, 23:491.
18. W.D. Phllips, H.J. Metcalf. Laser cooling and electromagnetic trapping of neutral atoms., J.Opt.Soc.Am,B, 1985, 2:1751
19. A. Aspect, J. Dalibard, A. Heidmann,et al. Cooling atoms with stimulated emission., Phys.Rev.Lett., 1986, 57:1688.
20. David G. Grier, A revolution in optical manipulation. Nature, 2003, 424:810.
21. A. Ashkin, Acceleration and trapping of particles by radiation pressure, Phys.Rev.Lett., 1970, 24:156-159.
22. A. Ashkin and J.M.Dziedzic, Optical levitation of liquid drops by radiation pressure, Science, 1975, 187:1073-1075.
23. Ashkin, A. & Dziedzic, J. M., Optical levitation in high-vacuum. Appl. Phys. Lett. , 1976, 28:333–335.
24. Ashkin, A. & Dziedzic, J. M. Feedback stabilization of optically levitated particles. Appl.Phys. Lett. 1977, 30: 202–204
25. A. Ashkin, Observation of Light Scattering from Nanospherical Particles Using Optical Levitation, Appl. Optics, 1980, 19: 660.
26. Haowei Wang, Xiaohui Liu, Yinmei Li. Isolation of a single rice chromosome by optical micromanipulation. J.Opt. A: Pure Appl. Opt, 2004, 6:89.
27.王浩威,刘晓辉,李银妹等,应用光学微操作技术分选单条水稻染色体。生物物理学报,2004,20:50.
28. K. Visscher, M. J. Schnitzer, S. M. Block, Single Kinesin Molecules Studied with a Molecular Force Clamp. Nature, 1999, 400:184.
29. K. Svoboda, C. F. Schmidt, S. M. Block, Direct Observation of Kinesin Stepping by Optical Trapping Interferometry. Nature, 1993, 365:721-727
30. Mark J. Schnitzer, Steven, M. Block, Kinesin Hydrolyses one ATP per 8-nm Step. Nature, 1997, 388:386
31. Mark J. Schnitzer, Koen Visscher, Steven, M. Block, Force Production by Single KinesinMotors. Nature Cell Biology, 2000, 2:718.
32. Miklos S. Z. Kellermayer, Steven B. Smith, Henk L. Granzier, Folding-Unfolding Transitions in Single Titin Molecules Characterized with Laser Tweezers. Science, 1997, 276:1112-1116
33. Miklos S. Z. Kellermayer, Steven B. Smith, Carlos Bustamante, Mechaniccal Fatigue in repetitively Stretched Single Molecules of Titin. Biophysical Journal, 2001, 80:852-863.
34. Xiaohui Zhang, Kenneth Halvorsen, Timothy A. Springer et.al. Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand Factor, Science, 2009, 324:1330-1334.
1. Trinchieri , G. Adv. Immunol. 1989 47:187–376.
2.金伯泉.细胞与分子免疫学[M].世界图书出版公司,1995:259-274
3. Gμmperz , J.E., and P. Parham. Nature. 1995 378: 245-248.
4. Ryan, J.C., E.C. Niemi el. J. Exp. Med. 1995 181:1911–1915.
5. Lanier, L.L. Curr. Opin. Immunol. 1997 9:126–131.
6. Yokoyama, W.M. Curr. Opin. Immunol.1998 10:298–305.
7. Marcenaro E et al, Eur J Immunol, 2003,33(12):3367-3376
8. Natarajan K, Dimasi N, Wang J,et al. Annu Rev Immunol, 2002,20,853
9. Moretta L, Bottino C, Pende D, et al. Eur J Immunol, 2002,32:1025
10.田志刚,魏海明等.中国免疫学杂志2004 20:33-35
11. Niwa R, Sakurada M, Kobayashi Y etal. Clin Cancer Res, 2005, 11(6): 2327-2336
12. Smyth M J, Cretney E, Kelly J M etal. Mol Immunol, 2005, 42:501-510.
13. Zompi S, Colucci F. Immunology Letters, 2005, 97:31-39.
14. Agerberth B, Charo J, Werr K etal. Blood, 2000, 96: 3086-3093.
15. Aurelie Wiedemann, Davie Depoil. 2006. Proc. Natl. Acad. Sci. USA. 103: 10985-10990.
16. Paul A.Negulescu el. Immunity, 1996 Vol. 4, 421-430.
17. Mikael Eriksson el.,Journal of Experimental Medicine 1999 7:1005-1012s
1. Lo CG, Lu TT, Cyster JG. Integrin-dependence of Iymphocyte entry into the splenic white pulp[J]. J Exp Med, 2003, 197:353-361.
2. Riaz AA, Wan MX, Schaefer T, et al. Fundamental and distinctroles of P-selectin and LFA-1 in ischemia/ reperfusion-induced leukocyte- endothelium interactions in the mouse colon[J]. Ann Surg, 2002, 236:777-784.
3. Melero, I., M.A. Balboa, J.L. Alonso, et al. Signaling through the LFA-1 leucocyte integrin actively regulates intercellular adhesion and tumor necrosis factor-alpha production in natural killer cells. European Journal of Immunology. 1993, 23(8): 1859-1865.
4. Sugie, K., Y. Minami, T. Kawakami, et al. Stimulation of NK-like YT cells via leukocyte function-associated antigen (LFA)-1. Possible involvement of LFA-1-associated tyrosine kinase in signal transduction after recognition of NK target cells. Journal of Immunology. 1995, 154(4): 1691-1698.
5. Luo, D., D. Vermijlen, K. Vanderkerken, et al. Involvement of LFA-1 in hepatic NK cell (pit cell)-mediated cytolysis and apoptosis of colon carcinoma cells. Journal of hepatology. 1999, 31(1): 110-116
6. Matsumoto, G., Y. Omi, U. Lee, et al. Adhesion mediated by LFA-1 is required for efficient IL-12-induced NK and NKT cell cytotoxicity. European Journal of Immunology. 2000, 30(12): 3723-3731
7. Borthwick NJ, Akbar AA, Buckley C, et al. Transendothelial migration a survival advantage to activated T lymphocytes: role of LFA-1/ICAM-1 interactions[J]j. Clin Exp Immunol, 2003, 134:246-252.
8. Richardson BC. Role of DNA methylation in the regulation of cell function: autoimmunity, aging and cancer[J]. J Nutr, 2002, 132:2401S-2405S.
9. Bangs Laboratoried, Inc. Covalent coupling, TechNote, 2002, 205:1-8.
10. H.T. Chen, Y.M.Li, L.R.Lou, et al. Single molecules detection in optical tweezers. Xing Zhu. Nano-Optics and Nano-Structures, Proceedings of SPIE Vol. 4923, 98-105.
11. Robert M.Simmons, J.T.Finer, S.Chu etc.“Quantitative Measurements of Force andDisplacement Using an Optical Trap,”J.Biophysical Journal, 1996, 70,1813-1822
12. Karl Otto Greulich. Micromanipulation by light in biology and medicine: the laser microbeam and optical tweezers.Berlin:Birkhauser Verlag, 1999, 90-96.
13. Florin E.-L., Pralle A., Stelzer E.H.K., et al.“Photonic force microscope calibration by thermal noise analysis,”J. Appl. Phys. A, 1998, 66, S75-S78 .
14.龚錾,陈洪涛,李银妹,四种光阱刚度测量法的实验研究与比较。中国科大学报,2005, 35:601。
1.易仁亮,邹霞英.红细胞变形性的影响因素[J].中国病理生理杂志,1995,11(6):658-659
2.范家骏,赵国欣.血液流变学基础与临床[M].陕西科学技术出版社,1995,1.
3.刘凝慧,祁友键21种不同纲脊椎动物红细胞变形能力的测量[J].徐州医学院学报,1989,9(3),181-185
4.尹翠娥.红细胞变形性的研究进展.重庆医学,1997,26(2):81-83
5.王红勇,何作云,李希楷冠心病患者红细胞变形性和全血粘弹性的变化.中华老年医学杂志,2001,20(6):455-456
6.何作云,王瑞兴.临床细胞流变学[M].重庆大学出版社,1997
7. Bessis M, Mohandas N A, Claude Feo. Automated ektacytometry: a new method of measuring red cell deformability and red cell indices. Blood Cell, 1980, 6:315-327
8. Fieger R , Grebe R. Cell-elastometry: a new method to measure erythrocyte elasticity. Biorheology , 1997 , 34 (3) : 223-291
9. Wen Zongyao , Yan Zonggyi , Gao Tie , et al. The study of effects of WGA and ConA on RBC receptors with a new Ektacytometry. Clinical and Microcirculation , 1997 ,17(6) :467～478
10.文宗曜,严宗毅,施岩等.测量红细胞膜剪切弹性模量及粘度的新方法,清华大学出版社,1997 ,741-744.
11.严宗毅.测量红细胞变形性的新方法[J].国外医学生物医学工程分册,1997,20(5):257-263
12.王玉英,王益民,史红.激光衍射法测量红细胞变形原理及有关问题分析[J].天津中医学院学报,2003,22(2):66-67
13. Shin S, Ku Y. Disposable laser-diffraction ektacytometry to measure red blood cell deformability[J]. Progress in Biomedical Optics and Imaging-Proceedings of SPIE, 2005, 5630(1): 168-176
14. Magus I. Gregersen, Cyrus A. Bryant, Walter E. Hammerle, Shunichi Usami and Shu Chien. Flow characteristics of human erythrocytes through polycarbonate sieves. Science,1967, 157(3790):825-827
15.王怡实用临床血液流变学,学苑出版社,1994,113-115
16. Micthison JM, Swann MM. The mechinical properties of the red cell surface[J]. J Exp Biol, 1954, 31:443-460
17. Lacelle PL. Effect of sphering on erythrocyte deformability. Biorheology. 1972, 9(2):51-59
18. Rand RP, Burton AC. Mechinical properties of red cell membrane[J]. Biophys J, 1964,4:115-135
19. Evans E.A., 1973. New membrane concept applied to the analysis of fluid shear-and micropipette-deformed red blood cells. Biophys. J. 13(9), 941-954.
20. Evans E.A., Waugh R. 1977. Osmotic correction to elastic area compressibility measurements on red cellmembrane. Biophys. J. 20:307
21. Ashkin A. Optical trapping and manipulation of single cells using infrared laser beams. Nature, 1987, 330:769-771
22. Svoboda K. Biological applications of optical forces. Annu Rev Biophys Biomol Struct, 1994, 23:247-285
23. Sheetz MP. Laser tweezers in cell biology. London, UK: Academic Press; 1998
24. Sylvie He′non, Guillanme Lenormand, Alain Richert and Francois Gallet. A new determination of shear modulus of the human erythrocyte membrane using optical tweezers. 1999, 76:1145-1151
25.周辉,李先锋,李银妹等.单光镊技术测量红细胞膜弹性新方法的建立.生物化学与生物物理进展,2001,28(6):904-907
26. Guillaume Lenormand. Direct measurement of the area expansion and shear module of the human red cell membrane skeleton. Biophysical Journal. 1999, 81:43-56
27. John Sleep, David Wilson, Robert Simmons, and Walter Gratzer. Elasticty of the red cell membrane and its relation to Hemolytic disorders: An optical tweezers study. Biophysical Journal. 1999, 77:3085-3095.
1. Ren Hongliang, Zhuang Lihui, Li Yinmei. Measurement of interaction potential between colloidal particles using dual optical tweezers. Chinese J. Lasers, 2008, 35(1):151-155
2. Furst EM. Applications of laser tweezers in complex fluid rheology[J]. Current Opinion in Colloid & Interface Science. 2005, 10: 79-86.
3. Dame RT, Noom MC, Wuite GJL. Bacterial chromatin organization by H-NS protein unravelled using dual DNA manipulation[J]. Nature. 2006, 444(16): 387-340.
4. Finer JT, Simmons RM, Spudich JA. Single myosin molecule mechanics: piconewton forces and nanometre steps[J]. Nature. 1994, 368: 113-119.
5. Guan Bo Liao, Paul B. Bareil, Arthur Chiou. et al. One-dimensional jumping optical tweezers for optical stretching of bi-concave human red blood cells. Optical Society of America. 2008, 16(3): 1996-2004.
6.陈洪涛.纳米光镊技术研究,2003,中国科学技术大学博士学位论文。
7. J.P.Pantina and E.M.Furst,“Directed assembly and rupture mechanics of colloidal aggregates,”Langmuir 20, 3940-3946 (2004).
8. Dufresne E.R., Grier D.G.. Optical tweezers and optical substrates created with diffractive optics.[J]. Rev. Sci. Instr., 1998, 69(5): 1974-1977.
9. Jesacher A., Furhapter S., Bernet S. et al. Diffractive optical tweezers in the Fresnel regime [J]. Opt. Exp., 2004, 12(10): 2243-2250.
10. Grier D.G.. A revolution in optical manipulation[J]. Nature, 2003, 424(6950): 810-816.
11. Grier D.G.. Roichma Y.. Holographic optical trapping[J]. Appl. Opt., 2006, 45(5): 880-887.
12. Roichman Y., Sun B. et al.. Optical forces arising from phase gradients[J]. Phys. Rev. Lett., 2008, 100(1): 013602.
13. Curtis JE, Koss BA, Grier DG. Dynamic holographic optical tweezers[J]. Opt. Commun. 2002, 207: 169-175.
14. Jesacher A, Maurer C, Fürhapter S et al. Optical tweezers of programmable shape with transverse scattering forces[J]. Opt. Commun. 2008, (281): 2207-2212.
15.任煜轩,周金华,吴建光等.全息光镊-光镊家族中极具活力的成员[J].激光与光电子学进展. 2008, 45(11): 35-41.
16.庄礼辉,任洪亮,李银妹等。同步斩波法测量胶体粒子间相互作用势,应用激光,2007,27:132-135.
17. J.P.Pantina and E.M.Furst,“Elasticity and critical bending moment of model colloidal aggregates,”Phys.Rev.Lett. 94, 138301 (2005).
18. Pleguezuelos E., Carnicer A., Andilla J. et.al.. Holotrap: Interactive hologram design for multiple dynamic optical trapping[J]. Computer Phys. Comm., 2007, 176:701-709.
19. Curtis J.E., Koss B.A., Grier D.G.. Dynamic holographic optical tweezers[J]. Opt. Comm., 2002, 207: 169-175.
20. Jesacher A., Maurer C., Furhapter S. et al.. Optical tweezers of programmable shape with transverse scattering forces[J]. Opt. Comm., 2008, 281: 2207-2212.
21. BingHuan Meng, JinHua Zhou, JianGuang Wu. et al. Inprovement of transverse trapping efficiency of optical tweezers[J]. Chin. Phys. Lett. 2008, 25(6): 2300-2302.
22.李银妹,楼立人,姚媛等.光阱阱位的观察与调节[J].中国激光Chinese Journal of Lasers. 1998, 25(12): 1083-1086.
23. Shenhua Xu, Yinmei Li, Liren Lou etc., Computer simulation of the collision frequency of two particles in optical tweezers. Chinese Physics, 2005, 14:382.
24. Zan Gong, Hongtao Chen, Shenghua Xu, Yinmei Li, Liren Lou. Monte-Carlo simulation of optical trap stiffness measurement. Optics Communications, 263(2), 229-234, 2006.
25.汪志诚.热力学与统计物理[M],北京:高等教育出版社,1980(2001年重印),P386.
1.司徒镇强,吴军正.细胞培养[M],世界图书出版公司,2007.
2.牟章兵,杜之渝,晏丕松.汉防己甲素等5种抗纤维化药物对离体HELA的抑制作用[J].眼科新进展,2006,26(8):592-596.
3. Grad JM, Bahlis NJ, Reis I, etal. Ascorbic acid enhances As2O3-induced cytotoxicity in multiple myeloma cells[J]. Blood, 2001,98(3): 805-813.
4.李新宇,李贵刚,朱雪菲.Bcl2xl/Lipofectamine2000比值对人HELA转染效率的影响[J].眼科新进展,2006,27(7):524-526.