核酸与蛋白质相互作用的AFM单分子力谱研究
|
摘要
核酸与蛋白质是组成生命的主要生物大分子,二者的相互作用构成了诸如生长、繁殖、遗传和代谢等生命现象的基础。从单分子水平上对它们的相互作用进行纳米探测,有利于人们更加深入地理解与调控这些重要的生理过程,是人们解开生命奥秘的关键所在。基于原子力显微镜的单分子力谱技术是一种非常有效的研究分子间/分子内相互作用的方法。本论文首先对单分子力谱的原理和它在生物学领域的应用进行了总结,然后通过对两个核酸-蛋白质体系的研究利用并发展了该力谱方法。这两个核酸-蛋白质体系分别为：(1)长链双螺旋DNA与SSB蛋白(2)烟草花叶病毒中基因组RNA与衣壳蛋白之间的相互作用。本论文的工作围绕以上两个体系并遵从由简入繁的原则展开：
一、研究了双螺旋DNA在外力诱导下构象转变的本质以及单股DNA与SSB蛋白的相互作用。以长链双螺旋DNA作为探针,利用单分子力谱的方法并结合单股DNA结合蛋白(SSB)只与单股DNA结合而不与双螺旋DNA结合的特性,研究了双螺旋DNA在较低外力(65 pN左右)诱导下构象转变的本质。
二、以更加复杂的完整烟草花叶病毒(TMV)为模型体系,研究基因组RNA与衣壳蛋白之间的相互作用。我们首次将RNA从TMV颗粒中牵拉出来,直接定量测得了基因组RNA与衣壳蛋白之间的结合强度,并证明衣壳蛋白保留在TMV蛋白外壳上而没有随RNA一同被牵拉出来。当外力被撤销后部分RNA能够重新组装回到TMV的蛋白外壳中。
三、在上述工作基础上,更加深入地对RNA与衣壳蛋白解离的动力学过程进行了研究。通过测量在不用的pH值及外力加载速率下RNA与衣壳蛋白的断裂力,来描述RNA与衣壳蛋白断裂过程的能垒,获得其动力学信息,揭示RNA从蛋白外壳上解组装的机制。合强度,并证明了衣壳蛋白保留在TMV蛋白外壳中而没有随RNA一同被牵拉出来。当外力被撤销后部分RNA在位于5’端较远的、没有被破坏的RNA-蛋白外壳复合物的作用下,能够重新组装回到TMV的蛋白外壳中。我们还初步考察了环境因素,比如缓冲溶液中的EDTA浓度、pH值以及外力加载速率对RNA与衣壳蛋白相互作用的影响。通过此研究我们将AFM单分子力谱方法拓展到相对复杂生物体系的核酸与蛋白质相互作用的研究中,同时有望将该技术应用到病毒感染机理的研究。
在本论文第四章中,仍以烟草花叶病毒为研究模型,更加深入、系统地对RNA与衣壳蛋白解离的动力学过程进行了研究。通过测量在不用加载速率下RNA与衣壳蛋白的断裂力,发现该断裂力是具有加载速率依赖性的。而且,Bell-Evans模型可以很好地拟合我们的实验数据,并给出了RNA与衣壳蛋白的断裂过程的动力学参数并且描述了断裂的能垒。在pH值为4.7的条件下RNA与衣壳蛋白的解离过程由一个能垒控制；在pH值为7.0的条件下断裂过程由两个能垒控制,增加的一个能垒来源于病毒颗粒内壁上无序的突环结构对RNA解离的阻碍作用。
Nucleic acids and proteins are two important biomacromolecules that compose the life, and the interactions between them are the base of many biological phenomena, such as growth, propagation, inheritance, metabolism, and so on. The nano-mechanical detection of nucleic acid-protein interactions at single-molecule level will deepen our understanding and eventually gain controls on these biological processes. This is also the key to explore the mysteries of life. Atomic force microscopy (AFM)-based single molecule force spectroscopy (SMFS) is a very effective technique for the investigation of inter- or intramolecular interactions.In chapter 1, the basic principle of SMFS is introduced in detail, including the analysis of a force curve, the criteria for single chain stretching and dynamic force spectroscopy (DFS). Some recent progresses in SMFS study of biological systems have also been summarized. In the later chapters, we investigated two nucleic acid and protein systems from relatively simple to complex one by using SMFS. These two systems are long double stranded DNA (dsDNA) and single-stranded DNA (ssDNA) binding protein (SSB), together with genetic RNA of tobacco mosaic virus (TMV) and its coat proteins, respectively.
In chapter 2, we have revealed the mechanism of force-induced conformation transition of dsDNA and the interactions between (single stranded DNA) ssDNA and SSB proteins. Taking advantage of the character that SSB proteins interact with ssDNA specifically but not with dsDNA, we used a long dsDNA as a probe to investigate the nature of force-induced conformation transition of dsDNA. Our results indicate that dsDNA is partially melted into ssDNA during the overstretching transition (i.e. dsDNA exist as a mixture of the dsDNA and molten ssDNA) at the mechanical force of about 65 pN, and the SSB proteins are able to capture the transient ssDNA fragments slowing down the rehybridization process, causing the hysteresis between stretching and relaxation traces. After relaxation, the SSB proteins can be removed from the ssDNA fragments, and the dsDNA recovers its B-form conformation. We have also systematically investigated the effects of stretching length, waiting time, and salt concentration on the conformation transition of dsDNA and SSB-ssDNA interactions, respectively. The study indicates that electrostatic interaction, intercalating interaction and hydrophobic interaction are the main driving forces for the formation of SSB-ssDNA complexes.
In chapter 3, we took a more complicated system, an intact tobacco mosaic virus (TMV), as a model to reveal the interactions between genetic RNA and coat proteins. For the first time, by using an AFM tip, we have pulled the genetic RNA step by step out of the helical groove formed by its protein coat, producing a sawtooth-like plateau, from which the quantitative unbinding force between the RNA and coat proteins is obtained. We have proved that the coat proteins stayed in the protein coat but not being pulled out together with RNA. When the external force is released, the detached RNA fragment can find its way back to the helical protein coat with the help of intact RNA-protein complexes located in the deeper part (i.e., away from the 5'end) of the TMV particle. We have also studied the effects of other factors such as EDTA concentration, pH value and loading rate on the interactions between RNA and coat proteins. The present study extends the force spectroscopy technique to the study of nucleic acid-protein interactions in more complicated biological systems. And the method established here may open a new door toward investigations of the mechanism of virus infection.
In chapter 4, we still took tobacco mosaic virus as a model system to investigate the dynamic process of RNA-coat protein interactions in more detail. We explored the dependence of unbinding forces of RNA-coat protein complexes on the loading rate, that is, the rate at which the force is applied to the binding. The experimental data can be fitted well by the Bell-Evans model, which enables us to determine the energy barrier width (xp), off-rate constant (koff), binding lifetime (τ) and to describe the energy landscape of RNA-coat protein interactions. The results show that at pH 4.7, the unbinding process is only dominated by one energy barrier stabilizing RNA-coat protein complexes, while at pH 7.0, the unbinding process is dominated by two energy barrier, the extra energy landscape comes from the disordered loop of polypeptide in the wall of the inner channel of TMV.
一、研究了双螺旋DNA在外力诱导下构象转变的本质以及单股DNA与SSB蛋白的相互作用。以长链双螺旋DNA作为探针,利用单分子力谱的方法并结合单股DNA结合蛋白(SSB)只与单股DNA结合而不与双螺旋DNA结合的特性,研究了双螺旋DNA在较低外力(65 pN左右)诱导下构象转变的本质。
二、以更加复杂的完整烟草花叶病毒(TMV)为模型体系,研究基因组RNA与衣壳蛋白之间的相互作用。我们首次将RNA从TMV颗粒中牵拉出来,直接定量测得了基因组RNA与衣壳蛋白之间的结合强度,并证明衣壳蛋白保留在TMV蛋白外壳上而没有随RNA一同被牵拉出来。当外力被撤销后部分RNA能够重新组装回到TMV的蛋白外壳中。
三、在上述工作基础上,更加深入地对RNA与衣壳蛋白解离的动力学过程进行了研究。通过测量在不用的pH值及外力加载速率下RNA与衣壳蛋白的断裂力,来描述RNA与衣壳蛋白断裂过程的能垒,获得其动力学信息,揭示RNA从蛋白外壳上解组装的机制。合强度,并证明了衣壳蛋白保留在TMV蛋白外壳中而没有随RNA一同被牵拉出来。当外力被撤销后部分RNA在位于5’端较远的、没有被破坏的RNA-蛋白外壳复合物的作用下,能够重新组装回到TMV的蛋白外壳中。我们还初步考察了环境因素,比如缓冲溶液中的EDTA浓度、pH值以及外力加载速率对RNA与衣壳蛋白相互作用的影响。通过此研究我们将AFM单分子力谱方法拓展到相对复杂生物体系的核酸与蛋白质相互作用的研究中,同时有望将该技术应用到病毒感染机理的研究。
在本论文第四章中,仍以烟草花叶病毒为研究模型,更加深入、系统地对RNA与衣壳蛋白解离的动力学过程进行了研究。通过测量在不用加载速率下RNA与衣壳蛋白的断裂力,发现该断裂力是具有加载速率依赖性的。而且,Bell-Evans模型可以很好地拟合我们的实验数据,并给出了RNA与衣壳蛋白的断裂过程的动力学参数并且描述了断裂的能垒。在pH值为4.7的条件下RNA与衣壳蛋白的解离过程由一个能垒控制；在pH值为7.0的条件下断裂过程由两个能垒控制,增加的一个能垒来源于病毒颗粒内壁上无序的突环结构对RNA解离的阻碍作用。
Nucleic acids and proteins are two important biomacromolecules that compose the life, and the interactions between them are the base of many biological phenomena, such as growth, propagation, inheritance, metabolism, and so on. The nano-mechanical detection of nucleic acid-protein interactions at single-molecule level will deepen our understanding and eventually gain controls on these biological processes. This is also the key to explore the mysteries of life. Atomic force microscopy (AFM)-based single molecule force spectroscopy (SMFS) is a very effective technique for the investigation of inter- or intramolecular interactions.In chapter 1, the basic principle of SMFS is introduced in detail, including the analysis of a force curve, the criteria for single chain stretching and dynamic force spectroscopy (DFS). Some recent progresses in SMFS study of biological systems have also been summarized. In the later chapters, we investigated two nucleic acid and protein systems from relatively simple to complex one by using SMFS. These two systems are long double stranded DNA (dsDNA) and single-stranded DNA (ssDNA) binding protein (SSB), together with genetic RNA of tobacco mosaic virus (TMV) and its coat proteins, respectively.
In chapter 2, we have revealed the mechanism of force-induced conformation transition of dsDNA and the interactions between (single stranded DNA) ssDNA and SSB proteins. Taking advantage of the character that SSB proteins interact with ssDNA specifically but not with dsDNA, we used a long dsDNA as a probe to investigate the nature of force-induced conformation transition of dsDNA. Our results indicate that dsDNA is partially melted into ssDNA during the overstretching transition (i.e. dsDNA exist as a mixture of the dsDNA and molten ssDNA) at the mechanical force of about 65 pN, and the SSB proteins are able to capture the transient ssDNA fragments slowing down the rehybridization process, causing the hysteresis between stretching and relaxation traces. After relaxation, the SSB proteins can be removed from the ssDNA fragments, and the dsDNA recovers its B-form conformation. We have also systematically investigated the effects of stretching length, waiting time, and salt concentration on the conformation transition of dsDNA and SSB-ssDNA interactions, respectively. The study indicates that electrostatic interaction, intercalating interaction and hydrophobic interaction are the main driving forces for the formation of SSB-ssDNA complexes.
In chapter 3, we took a more complicated system, an intact tobacco mosaic virus (TMV), as a model to reveal the interactions between genetic RNA and coat proteins. For the first time, by using an AFM tip, we have pulled the genetic RNA step by step out of the helical groove formed by its protein coat, producing a sawtooth-like plateau, from which the quantitative unbinding force between the RNA and coat proteins is obtained. We have proved that the coat proteins stayed in the protein coat but not being pulled out together with RNA. When the external force is released, the detached RNA fragment can find its way back to the helical protein coat with the help of intact RNA-protein complexes located in the deeper part (i.e., away from the 5'end) of the TMV particle. We have also studied the effects of other factors such as EDTA concentration, pH value and loading rate on the interactions between RNA and coat proteins. The present study extends the force spectroscopy technique to the study of nucleic acid-protein interactions in more complicated biological systems. And the method established here may open a new door toward investigations of the mechanism of virus infection.
In chapter 4, we still took tobacco mosaic virus as a model system to investigate the dynamic process of RNA-coat protein interactions in more detail. We explored the dependence of unbinding forces of RNA-coat protein complexes on the loading rate, that is, the rate at which the force is applied to the binding. The experimental data can be fitted well by the Bell-Evans model, which enables us to determine the energy barrier width (xp), off-rate constant (koff), binding lifetime (τ) and to describe the energy landscape of RNA-coat protein interactions. The results show that at pH 4.7, the unbinding process is only dominated by one energy barrier stabilizing RNA-coat protein complexes, while at pH 7.0, the unbinding process is dominated by two energy barrier, the extra energy landscape comes from the disordered loop of polypeptide in the wall of the inner channel of TMV.
引文
1. Muller, D. J.; Dufrene, Y. F. Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology. Nat. Nanotechnol.2008,3,261-269.
2. Kufer, S. K.; Puchner, E. M.; Gumpp, H.; Liedl, T.; Gaub, H. E. Single-molecule cut-and-paste surface assembly. Science 2008,319,594-596.
3. Clausen-Schaumann, H.; Seitz, M.; Krautbauer, R,; Gaub, H. E. Force spectroscopy with single bio-molecules. Curr. Opin. Chem. Biol.2000,4, 524-530.
4.张文科,王驰,张希,单分子力谱,科学通报,2003,48,1113-1126.
5. Zhang, W. K.; Barbagallo, R.; Madden, C.; Roberts, C. J.; Woolford, A.; Allen, S. Progressing single biomolecule force spectroscopy measurements for the screening of DNA binding agents. Nanotechnology 2005,16,2325-2333.
6. Janshoff, A.; Neitzert, M.; Oberdorfer, Y.; Fuchs, H. Force spectroscopy of molecular systems-single molecule force spectroscopy of polymers and biomolecules. Angew. Chem., Int. Ed.2000,39,3212-3237.
7. Hugel, T.; Seitz, M. The study of molecular interactions by AFM force spectroscopy. Macromol. Rapid Commun.2001,22,989-1016.
8.刘传军,大分子与小分子间相互作用的单分子力谱研究,吉林大学博士学位论文,2007.
9. Liu, K.; Song, Y.; Feng, W.; Liu, N. N.; Zhang, W. K.; Zhang, X. Extracting a single polyethylene oxide chain from a single crystal by a combination of atomic force microscopy imaging and single-molecule force spectroscopy:Toward the investigation of molecular interactions in their condensed states. J. Am. Chem. Soc.2011,133,3226-3229.
10. Li, H. B.; Liu, B. B.; Zhang, X.; Gao, C. X.; Shen, J. C.; Zou, G. T. Single-molecule force spectroscopy on poly(acrylic acid) by AFM. Langmuir 1999,15,2120-2137.
11. Hugel, T.; Grosholz, M.; Clausen-Schaumann, H.; Pfau, A.; Gaub, H. E.; Seitz, M. Elasticity of single polyelectrolyte chains and their desorption from solid supports studied by AFM based single molecule force spectroscopy. Macromolecules 2001, 34,1039-1047.
12. Rief, M.; Oesterhelt, F.; Heymann, B.; Gaub, H. E. Single molecule force spectroscopy on polysaccharides by atomic force microscopy. Science 1997,275, 1295-1297.
13. Zhang, W. K.; Xu, Q. B.; Zou, S.; Li, H. B.; Xu, W. Q.; Zhang, X.; Shao, Z. Z.; Kudera, M.; Gaub, H. B. Single-molecule force spectroscopy on bombyx mori silk fibroin by atomic force microscopy Langmuir 2000,16,4305-4308.
14. Zhang, W. K.; Zhang, X. Single molecule mechanochemistry of macromolecules. Prog. Polym. Sci.2003,28,1271-1295.
15. Zou, S.; Zhang, W. K.; Zhang, X.; Jiang, B. Z. Study on polymer micelles of hydrophobically modified ethyl hydroxyethyl cellulose using single-molecule force spectroscopy. Langmuir 2001,17,4799-4808.
16.王驰,聚丙烯酰胺衍生物的单链拉伸AFM研究,吉林大学硕士学位论文,2003.
17.张文科,单分子纳米力学探测,吉林大学博士学位论文,2002.
18. Cui, S. X.; Liu, C. J.; Zhang, X. Simple method to isolate single polymer chains for the direct measurement of the desorption force. Nano Letters 2003,3,245-248.
19.崔树勋,高分子界面吸附的单分子力谱研究,吉林大学博士学位论文,2004.
20. Evans, E. Energy landscapes of biomolecular adhesion and receptor anchoring at interfaces explored with dynamic force spectroscopy. Faraday Discuss.1998,111, 1-16.
21. Merkel, R.; Nassoy, P.; Leung, A.; Ritchie, K.; Evans, E. Energy landscpes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature 1999, 397,50-53.
22. Morfill, J.; Kuhner, F.; Blank, K.; Lugmaier, R. A.; Sedlmair, J.; Gaub, H. E. B-S transition in short oligonucleotides. Biophysical Journal 2007,93,2400-2409.
23. Dietz, H.; Rief, M. Exploring the energy landscape of GFP by single-molecule mechanical experiments. Proc. Nad. Acad. Sci. U.S.A.2004,101,16192-16197.
24. Best, R. B.; Fowler, S. B.; Toca-Herrera, J. L.; Clarke, J. A simple method for probing the mechanical unfolding pathway of proteins in detail. Proc. Natl. Acad. Sci. U.S.A.2002,99,12143-12148.
25. Evans, E. A.; Calderwood, D. A. Forces and bond dynamics in cell adhesion. Science 2007,316.1148-1153.
26. Bell, G. I. Models for the specific adhesion of cells to cells. Science 1978,200, 618-627.
27. Evans, E.; Ritchie, K. Dynamic strength of molecular adhesion bonds. Biophysical Journal 1997,72,1541-1555.
28. Rief, M.; Clausen-Schaumann, H.; Gaub, H. E. Sequence-dependent mechanics of single DNA molecules. Nat. Struct. Biol.1999,6,346-349.
29. Clausen-Schaumann, H.; Rief, M.; Tolksdorf, C.; Gaub, H. E. Mechanical stability of single DNA molecules. Biophys. J.2000,78,1997-2007.
30. Krautbauer, R.; Fischerlander, S.; Allen, S.; Gaub, H. E. Mechanical fingerprints of DNA drug complexes. Single Mol.2002,3,97-103.
31. Krautbauera, R.; Popeb, L. H.; Schradera, T. E.; Allenb, S.; Gaub, H. E. Discriminating small molecule DNA binding modes by single molecule force spectroscopy. FEBS Letters 2002,510,154-158.
32. Zhang, W. K.; Machon, C.; Orta, A.; Phillips, N.; Roberts, C. J.; Allen, S.; Soultanas, P. Single-molecule atomic force spectroscopy reveals that DnaD forms scaffolds and enhances duplex melting. J. Mol. Biol.2008,377,706-714.
33. Krasnoslobodtsev, A. V.; Shlyakhtenko, L. S.; Lyubchenko, Y. L. Probing interactions within the synaptic DNA-Sfil complex by AFM force spectroscopy. J. Mol. Biol.2007,365,1407-1416.
34. Kuhner, F.; Costa, L. T.; Bisch, P. M.; Thalhammer, S.; Heckl, W. M.; Gaub, H. E. LexA-DNA bond strength by single molecule force spectroscopy. Biophysical Journal 2004,87,2683-2690.
35. Wollschlager, K.; Gaus, K.; Kornig, A.; Eckel, R.; Wilking, S.-D.; Mclntosh, M.; Majer, Z.; Becker, A.; Ros, R.; Anselmetti, D.; Sewald, N. Single-molecule experiments to elucidate the minimal requirement for DNA recognition by transeription factor epitopes. Small 2009,5,484-495.
36. Rief, M.; Gautel, M.; Oesterhelt, F.; Fernandez, J. M.; Gaub, H. E, Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 1997, 276,1109-1112.
37. Marszalek, P. E.; Lu, H.; Li, H. B.; Carrion-Vazquez, M.; Oberhauser, A. F.; Schulten, K.; Fernandez, J. M. Mechanical unfolding intermediates in titin modules. Nature 1999,402,100-103.
38. Oberhauser, A. F.; Marszalek, P. E.; Carrion-Vazquez, M.; Fernandez, J. M. Single protein misfolding events captured by atomic force microscopy. Nat. Struct. Biol.1999,6,1025-1028.
39. Carrion-Vazquez, M.; Marszalek, P. E.; Oberhauser, A. F.; Fernandez, J. M. Atomic force microscopy captures length phenotypes in single proteins. Proc Natl. Acad. Sci. U.S.A.1999,96,11288-11292.
40. Carrion-Vazquez, M.; Oberhauser, A. F.; Fowler, S. B.; Marszalek, P. E.; Broedel, S. E.; Clarke, J.; Fernandez, J. M. Mechanical and chemical unfolding of a single protein:a comparison. Proc. Natl. Acad. Sci. U.S.A.1999,96,3694-3699.
41. Yang, G. L.; Cecconi, C.; Baase, W. A.; Vetter, I. R.; Breyer, W. A.; Haack, J. A.; Matthews, B. W.; Dahlquist, F. W.; Bustamante, C. Solid-state synthesis and mechanical unfolding of polymers of T4 lysozyme. Proc. Natl. Acad. Sci. U.S.A. 2000,97,139-144.
42. Dietz, H.; Rief, M. Exploring the energy landscape of GFP by single-molecule mechanical experiments. Proc. Natl. Acad. Sci. U.S.A.2004,101,16192-16197.
43. Puchner, E. M.; Gaub, H. E. Exploring the conformation-regulated function of titin kinase by mechanical pump and probe experiments with single molecules. Angew. Chem. Int. Ed.2010,49,1-5.
44. Brockwell, D. J.; Paci, E.; Zinober, R. C.; Beddard, G. S.; Olmsted, P. D.; Smith, D. A.; Perham, R. N.; Radford, S. E. Pulling geometry defnes the mechanical resistance of a beta-sheet protein. Nature Struct. Biol.2003,10,731-737.
45. Carrion-Vazquez, M.; Li, H. B.; Lu, H.; Marszalek, P. E.; Oberhauser, A. F. Fernandez, J. M. The mechanical stability of ubiquitin is linkage dependent. Nature Struct. Biol.2003,10,738-743.
46. Dietz, H.; Berkemeier, F.; Bertz, M.; Rief, M. Anisotropic deformation response of single protein molecules. Proc. Natl. Acad. Sci. U.S.A.2006,103, 12724-12728.
47. Oesterhelt, F.; Oesterhelt, D.; Pfeiffer, M.; Engel, A.; Gaub, H. E.; Muller, D. J. Unfolding pathways of individual bacteriorhodopsins. Science 2000,288, 143-146.
48. Kedrov, A.; Janovjak, H.; Sapra, K. T.; Muller, D. J. Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy. Annu. Rev. Biophys. Biomol. Struct.2007,36,233-260.
49. Kedrov, A.; Krieg, M.; Ziegler, C.; Kuhlbrandt, W.; Muller, D. J. Locating ligand binding and activation of a single antiporter. EMBO reports 2005,6,668-674.
50. Kedrov, A.; Ziegler, C.; Muller, D. J. Differentiating ligand and inhibitor interactions of a single antiporter. J. Mol. Biol.2006,362,925-932.
51. Kedrov, A.; Appel, M.; Baumann, H.; Ziegler, C.; Muller, D. J. Examining the dynamic energy landscape of an antiporter upon inhibitor binding. J. Mol. Biol. 2008,375,1258-1266.
52. Rief, M.; Oesterhelt, F.; Heymann, B.; Gaub, H. E. Single molecule force spectroscopy on polysaccharides by atomic force microscopy. Science 1997,275, 1295-1297.
53. Marszalek, P. E.; Oberhauser, A. F.; Pang, Y. P.; Pernandez, J. M. Polysaccharide elasticity governed by chair-boat transitions of glucopyranose ring. Nature 1998, 396,661-664.
54. Marszalek, P. E.; Pang, Y. P.; Li, H. B.; Yazal, J. E.; Oberhauser, A. F.; Pernandez, J. M. Atomic levers control pyranose ring conformations. Proc. Natl. Acad. Sci. U.S.A.1999,96,7894-7898.
55. Li, H. B.; Rief, M.; Oesterhelt, F.; Gaub, H. E.; Zhang, X.; Shen, J. C. Single-molecule force spectroscopy on polysaccharides by AFM:nanomechanical fingerprint of α-(1,4)-linked polysaccharides. Chem. Phys. Lett.1999,305, 197-201.
56. Xu, Q. B.; Zhang, W. K.; Zhang, X. Oxygen bridge inhibits conformational transition of 1,4-linked a-D-galactose detected by single-molecule atomic force microscopy. Macromolecules 2002,35,871-876.
57. Florin, E.-L.; Moy, V. T.; Gaub, H. E. Adhesion forces between individual ligand-receptor pairs. Science 1994,264,415-417.
58. Florin, E.-L.; Gaub, H. E. Intermolecular forces and energies between ligands and receptors. Science 1994,266,257-259.
59. Allen, S.; Chen, X. Y.; Davies, J.; Davies, M. C.; Dawkes, A. C.; Edwards, J. C.; Roberts, C. J.; Sefton, J.; Tendler, S. J. B.; Williams, P. M. Detection of antigen-antibody binding events with the atomic force microscope. Biochemistry 1997,36,7457-7463.
60. Hinterdorfer, P.; Baumgartner, W.; Gruber, H. J.; Schilcher, K.; Schindler, H. Detection and localization of individual antibody-antigen recognition events by atomic force microscopy. Proc. Natl. Acad. Sci. U.S.A.1996,93,3477-3481.
61. Morfill, J.; Neumann, J.; Blank, K.; Steinbach, U.; Puchner, E. M.; Gottschalk, K.-E.; Gaub. H. E. Force-based analysis of multidimensional energy landscapes: application of dynamic force spectroscopy and steered molecular dynamics simulations to an antibody fragment-peptide complex. J. Mol. Biol.2008,381, 1253-1266.
62. Benoit, M.; Gabriel, D.; Gerisch, G.; Gaub, H. E. Discrete interactions in cell adhesion measured by single-molecule force spectroscopy. Nature Cell Biology 2000,2,313-317.
63. Wojcikiewicz, E. P.; Abdulreda, M. H.; Zhang, X. H.; Moy, V. T. Force spectroscopy of LFA-1 and its ligands, ICAM-1 and ICAM-2. Biomacromolecules 2006,7,3188-3195.
64. Krieg, M.; Arboleda-Estudillo, Y.; Puech, P. H.; Kafer, J.; Graner, F.; Muller, D. J.; Heisenberg, C. P. Tensile forces govern germ-layer organization in zebrafish. Nature Cell Biology 2008,10,429-436.
65. Dupres, V.; Alsteens, D.; Andre, G.; Verbelen, C.; Dufrene, Y. F. Fishing single molecules on live cells. Nano Today 2009,4,262-268.
66. Alsteens, D.; Dupres, V.; Me Evoy, K.; Wildling, L.; Gruber, H. J; Dufrene, Y. F. Structure, cell wall elasticity and polysaccharide properties of living yeast cells, as probed by AFM. Nanotechnology 2008,19,384005(1-9).
67. Verbelen, C.; Dufrene, Y. F. Direct measurement of Mycobacterium-fibronectin interactions. Integr. Biol.2009,1,296-300.
68. Alsteens, D.; Dupres, V.; Klotz, S. A.; Gaur, N. K.; Lipke, P. N.; Dufrene, Y. F. Unfolding individual Als5p adhesion proteins on live cells. ACS Nano 2009,3, 1677-1682.
69. Rangl, M.; Nevo, R.; Liashkovich, I.; Shahin, V.; Reich, Z.; Ebner, A.; Hinterdorfer, P. Stable, non-destructive immobilization of native nuclear membranes to micro-structured PDMS for single-molecule force spectroscopy. ChemPhysChem 2009,10,1553-1558.
1. Krautbauera, R.; Popeb, L. H.; Schradera, T. E.; Allenb, S.; Gaub, H. E. Discriminating small molecule DNA binding modes by single molecule force spectroscopy. FEBS Letters 2002,510,154-158.
2. Williams, M. C.; Wenner, J. R.; Rouzina, I.; Bloomfield, V. A. Effect of pH on the overstretching transition of double-stranded DNA:Evidence of force-induced DNA melting. Biophys. J.2001,80,874-881.
3. Rouzina, I.; Bloomfield, V. A. Force-induced melting of the DNA double helix 1. Thermodynamic analysis. Biophys. J.2001,80,882-893.
4. Williams, M. C;. Rouzina, I.; Bloomfield, V. A. Thermodynamics of DNA interactions from single molecule stretching experiments. Ace. Chem. Res.2002, 35,159-166.
5. (a) McCauley, M. J.; Williams, M. C. Mechanisms of DNA binding determinded in optical tweezers experiments. Biopolymers 2007,85,154-168. (b) Shokri, L. Rouzina, I.; Williams, M. C. Interaction of bacteriophage T4 and T7 single-stranded DNA-binding proteins with DNA. Phys. Biol.2009,6, 025002(1-11). (c) Shokri, L.; Marintcheva, B.; Eldib, M.; Hanke, A.; Rouzina, I.; Williams, M. C. Kinetics and thermodynamics of salt-dependent T7 gene 2.5 protein binding to single- and double-stranded DNA. Nucl. Acids Res.2008,36, 5668-5677. (d) Shokri, L.; Marintcheva, B.; Richardson, C. C.; Rouzina, I.; Williams, M. C. Single molecule force spectroscopy of salt-dependent bacteriophage T7 gene 2.5 protein binding to single-strand DNA. J. Biol. Chem. 2006,281,38689-38696. (e) Pant, K.; Karpel, R. L.; Rouzina, I.; Williams, M. C. Salt dependent binding of T4 gene 32 protein to single and double-stranded DNA: single molecule force spectroscopy measurements. J. Mol. Biol.2005,349, 317-330. (f) Pant, K.; Karpel, R. L.; Rouzina, I.; Williams, M. C. Mechanical measurement of single-molecule binding rates:kinetics of DNA helix-destabilization by T4 gene 32 protein. J. Mol. Biol.2004,336,851-870. (g) Pant, K.; Karpel, R. L.; Williams, M. C. Kinetic regulation of single DNA molecule denaturation by T4 gene 32 protein structural domains. J. Mol. Biol.2003,327, 571-578. (h) Shokri, L.; McCauley, M. J.; Rouzina, I.; Williams, M. C. DNA overstretching in the presence of glyoxal:structural evidence of force-induced DNA melting. Biophys. J.2008,95,1248-1255.
6. Rief, M.; Clausen-Schaumann, H.; Gaub, H. E. Sequence-dependent mechanics of single DNA molecules. Nat. Struct. Biol.1999,6,346-349.
7. Clausen-Schaumann, H.; Rief, M.; Tolksdorf, C.; Gaub, H. E. Mechanical stability of single DNA molecules. Biophys. J.2000,78,1997-2007.
8. Ouzel, P.; Lebrun, A.; Heller, C.; Lavery, R.; Viovy, J.-L.; Chatenay, D.; Caron, F. DNA:an extensible molecule. Science 1996,271,792-794.
9. Smith, S. B.; Cui, Y. J.; Bustamante, C. Overstretching B-DNA:the elastic response of individual double-stranded and single-stranded DNA molecules. Science 1996,271,795-799.
10. Cocco, S.; Yan, J.; Leger, J.-F.; Chatenay, D.; Marko, J. F. Overstretching and force-driven strand separation of double-helix DNA. Phys. Rev. E 2004,70, 011910(1-18).
11. Zhou, H. J.; Zhang, Y.; Ou-Yang, Z. Bending and base-stacking interactions in double-stranded DNA. Phys. Rev. Lett.1999,82,4560-4563.
12. Chiang, K. N.; Yuan, C. A.; Han, C. N.; Chou, C. Y.; Cui, Y. J. Mechanical characteristic of ssDNA/dsDNA molecule under external loading. Appl. Phys. Lett.2006,88,023902(1-3).
13. Lebrun, A.; Lavery, R. Modelling extreme stretching of DNA. Nucleic Acids Res. 1996,24,2260-2267.
14. Zhang, W. K.; Dillingham, M. S.; Thomas, C.D.; Allen, S.; Roberts, C. J.; Soultanas, P. Directional loading and stimulation of PcrA helicase by the replication initiator protein RepD. J. Mol. Biol.2007,371,336-348.
15. Zhang,W. K.; Machon, C.; Orta, A.; Phillips, N.; Roberts, C. J.; Allen, S.; Soultanas, P. Single-molecule atomic force spectroscopy reveals that DnaD forms scaffolds and enhances duplex melting. J. Mol. Biol.2008,377,706-714.
16. Zhang, W. K.; Barbagallo, R.; Madden, C.; Roberts, C. J.; Woolford, A.; Allen, S. Progressing single biomolecule force spectroscopy measurements for the screening of DNA binding agents. Nanotechnology 2005,16,2325-2333.
17. Cubeddu, L.; White, M. F. DNA damage detection by an archaeal single-stranded DNA-binding protein. J. Mol. Biol.2005,353,507-516.
18. Bujalowski, W.; Lohman, T. M. Escherichia coli single-strand binding protein forms multiple, distinct complexes with single-stranded DNA. Biochemistry 1986, 25,7799-7802.
19. Kozlov, A. G.; Lohman, T. M. Stopped-flow studies of the kinetics of single-stranded DNA binding and wrapping around the Escherichia coli SSB tetramer. Biochemistry 2002,41,6032-6044.
20. Raghunathan, S.; Kozlov, A. G.; Lohman, T. M.; Waksman, G. Structure of the DNA binding domain of E. coli SSB bound to ssDNA. Nat. Struct. Biol.2000,7, 648-652.
21. Hatch, K.; Danilowicz, C.; Coljee, V.; Prentiss, M. Measurement of the salt-dependent stabilization of partially open DNA by Escherichia coli SSB protein. Nucleic Acids Res.2008,36,294-299.
22. Krautbauer, R.; Fischerlander, S.; Allen, S.; Gaub, H. E. Mechanical fingerprints of DNA drug complexes. Single Mol.2002,3,97-103.
1. Bawden, F. C.; Pirie, N. W.; Bernal, J. D.; Fankuchen, I. Liquid crystalline substances from virus-infected plants. Nature 1936,138,1051-1052.
2. Jonathan, P.; Butler, G. The current picture of the structure and assembly of tobacco mosaic virus. J. gen. Virol.1984,65,253-279.
3. Namba, K.; Stubbs, G. Structure of tobacco mosaic virus at 3.6 A resolution: implications for assembly. Science 1986,231,1401-1406.
4. Stubbs, G. Tobacco mosaic virus particle structure and the initiation of disassembly. Phil. Trans. R. Soc. London, Ser. B 1999,354,551-557.
5. Klug, A. The tobacco mosaic virus particle:structure and assembly. Phil. Trans. R. Soc. London, Ser. B 1999,354,531-535.
6. Sachse, C.; Chen, J. Z.; Coureux, P.-D.; Stroupe, M. E.; Fandrich, M.; Grigorieff, N. High-resolution electron microscopy of helical specimens:a fresh look at tobacco mosaic virus. J. Mol. Biol.2007,371,812-835.
7. Steckert, J. J.; Schuster, T. M. Sequence specificity of trinucleoside diphosphate binding to polymerized tobacco mosaic virus protein. Nature 1982,299,32-36.
8. Shaw, J. G. Tobacco mosaic virus and the study of early events in virus infections. Phil. Trans. R. Soc. London, Ser. B 1999,354,603-611.
9. Niu, Z. W.; Bruckman, M. A.; Li, S. Q.; Lee, A.; Lee, B.; Pingali, S. V.; Thiyagarajan, P.; Wang, Q. Assembly of tobacco mosaic virus into fibrous and macroscopic bundled arrays mediated by surface aniline polymerization. Langmuir 2007,23,6719-6724.
10. Royston, E.; Ghosh, A.; Kofinas, P.; Harris, M. T.; Culver, J. N. Self-assembly of virus-structured high surface area nanomaterials and their application as battery electrodes. Langmuir 2008,24,906-912.
11. Peng, B.; Liu, N. N.; Lin, Y.; Wang, L. M.; Zhang, W. K.; Niu, Z. W.; Wang, Q.; Su, Z. H. Self-assembly of anisotropic tobacco mosaic virus nanoparticles on gold substrate. Sci China Chem.2011,54,137-143.
12. Zhang, W. K.; Zhang, X. Single molecule mechanochemistry of macromolecules. Prog. Polym. Sci.2003,28,1271-1295.
13. Rief, M.; Clausen-Schaumann, H.; Gaub, H. E. Sequence-dependent mechanics of single DNA molecules. Nat. Struct. Biol.1999,6,346-349.
14. Cui, S. X.; Yu, J.; Kiihner, F.; Schulten, K.; Gaub, H. E. Double-stranded DNA dissociates into single strands when dragged into a poor solvent. J. Am. Chem. Soc.2007,129,14710-14716.
15. Smith, S. B.; Cui, Y. J.; Bustamante, C. Overstretching B-DNA:the elastic response of individual double-stranded and single-stranded DNA molecules. Science 1996,271,795-799.
16. Valle, F.; Zuccheri, G.; Bergia, A.; Ayres, L.; Rowan, A. E.; Nolte, R. J. M.; Samori, B. A polymeric molecular "handle" for multiple AFM-based single-molecule force measurements. Angew. Chem., Int. Ed.2008,47, 2431-2434.
17. Morfill, J.; Kuhner, F.; Blank, K.; Lugmaier, R. A.; Sedlmair, J.; Gaub, H. E. B-S Transition in Short Oligonucleotides. Biophysical Journal 2007,93,2400-2409.
18. Dietz, H.; Rief, M. Exploring the energy landscape of GFP by single-molecule mechanical experiments. Proc. Natl. Acad. Sci. U.S.A.2004,101,16192-16197.
19. Best, R. B.; Fowler, S. B.; Toca-Herrera, J. L.; Clarke, J. A simple method for probing the mechanical unfolding pathway of proteins in detail. Proc. Natl. Acad. Sci. U.S.A.2002,99,12143-12148.
20. Evans, E. Energy landscapes of biomolecular adhesion and receptor anchoring at interfaces explored with dynamic force spectroscopy. Faraday Discuss.1998,111, 1-16.
21. Merkel, R.; Nassoy, P.; Leung, A.; Ritchie, K.; Evans, E. Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature 1999, 397,50-53.
22. Zhang, W. K.; Zhang, X. Single molecule mechanochemistry of macromolecules. Prog. Polym. Sci.2003,28,1271-1295.
23. Namba, K.; Pattanayek, R.; Stubbs, G. Visualization of protein-nucleic acid interactions in a virus refined structure of intact tobacco mosaic virus at 2.9 A resolution by X-ray fiber diffraction. J. Mol. Biol.1989,208,307-325.
1. Steckert, J. J.; Schuster, T. M. Sequence specificity of trinucleoside diphosphate binding to polymerized tobacco mosaic virus protein. Nature 1982,299,32-36.
2. Bell, G. I. Models for the specific adhesion of cells to cells. Science 1978,200, 618-627.
3. Evans, E.; Ritchie, K. Dynamic strength of molecular adhesion bonds. Biophysical Journal 1997,72,1541-1555.
4. Niu, Z. W.; Bruckman, M. A.; Li, S. Q.; Lee, A.; Lee, B.; Pingali, S. V.; Thiyagarajan, P.; Wang, Q. Assembly of tobacco mosaic virus into fibrous and macroscopic bundled arrays mediated by surface aniline polymerization. Langmuir 2007,23,6719-6724.
5. Peng, B.; Liu, N. N.; Lin, Y.; Wang, L. M.; Zhang, W. K.; Niu, Z. W.; Wang, Q.; Su, Z. H. Self-assembly of anisotropic tobacco mosaic virus nanoparticles on gold substrate.Sci China Chem.2011,54,137-143.
6. Rief, M.; Fernandez, J. M.; Gaub, H. E. Elastically coupled two-level systems as a model for biopolymer extensibility. Phys. Rev. Lett.1998,81,4764-4767.
7. Jonathan, P.; Butler, G. The current picture of the structure and assembly of tobacco mosaic virus. J. gen. Virol.1984,65,253-279.
8. Namba, K.; Pattanayek, R.; Stubbs, G. Visualization of protein-nucleic acid interactions in a virus refined structure of intact tobacco mosaic virus at 2.9 A resolution by X-ray fiber diffraction. J. Mol. Biol.1989,208,307-325.
9. Yuan, C. B.; Chen, A.; Kolb, P.; Moy, V. T. Energy landscape of streptavidin-biotin complexes measured by atomic force microscopy. Biochemistry 2000,39, 10219-10223.
10. Piramowicz, M. D.; Czuba, P.; Targosz, M.; Burda, K.; Szymonski, M. Dynamic force measurements of avidin-biotin and streptavidin-biotin interactions using AFM. Acta Biochim. Polon.2006,53,93-100.
11. Bjornham, O.; Nilsson, H.; Andersson, M.; Schedin, S. Physical properties of the specific PapG-galabiose binding in E-coli P pili-mediated adhesion. European Biophysics Journal with Biophysics Letters 2009,38,245-254.
12. Yan, C.; Yersin, A.; Afrin, R.; Sekiguchi, H.; Ikai, A. Single molecular dynamic interactions between glycophorin A and lectin as probed by atomic force microscopy. Biophysical Chemistry 2009,144,72-77.
13. Bloomer, A. C.; Champness, J. N.; Bricogne, G.; Staden, R.; Klug, A. Protein disk of tobacco mosaic virus at 2.8 A resolution showing the interactions within and between subunits. Nature 1978,276,362-368.
2. Kufer, S. K.; Puchner, E. M.; Gumpp, H.; Liedl, T.; Gaub, H. E. Single-molecule cut-and-paste surface assembly. Science 2008,319,594-596.
3. Clausen-Schaumann, H.; Seitz, M.; Krautbauer, R,; Gaub, H. E. Force spectroscopy with single bio-molecules. Curr. Opin. Chem. Biol.2000,4, 524-530.
4.张文科,王驰,张希,单分子力谱,科学通报,2003,48,1113-1126.
5. Zhang, W. K.; Barbagallo, R.; Madden, C.; Roberts, C. J.; Woolford, A.; Allen, S. Progressing single biomolecule force spectroscopy measurements for the screening of DNA binding agents. Nanotechnology 2005,16,2325-2333.
6. Janshoff, A.; Neitzert, M.; Oberdorfer, Y.; Fuchs, H. Force spectroscopy of molecular systems-single molecule force spectroscopy of polymers and biomolecules. Angew. Chem., Int. Ed.2000,39,3212-3237.
7. Hugel, T.; Seitz, M. The study of molecular interactions by AFM force spectroscopy. Macromol. Rapid Commun.2001,22,989-1016.
8.刘传军,大分子与小分子间相互作用的单分子力谱研究,吉林大学博士学位论文,2007.
9. Liu, K.; Song, Y.; Feng, W.; Liu, N. N.; Zhang, W. K.; Zhang, X. Extracting a single polyethylene oxide chain from a single crystal by a combination of atomic force microscopy imaging and single-molecule force spectroscopy:Toward the investigation of molecular interactions in their condensed states. J. Am. Chem. Soc.2011,133,3226-3229.
10. Li, H. B.; Liu, B. B.; Zhang, X.; Gao, C. X.; Shen, J. C.; Zou, G. T. Single-molecule force spectroscopy on poly(acrylic acid) by AFM. Langmuir 1999,15,2120-2137.
11. Hugel, T.; Grosholz, M.; Clausen-Schaumann, H.; Pfau, A.; Gaub, H. E.; Seitz, M. Elasticity of single polyelectrolyte chains and their desorption from solid supports studied by AFM based single molecule force spectroscopy. Macromolecules 2001, 34,1039-1047.
12. Rief, M.; Oesterhelt, F.; Heymann, B.; Gaub, H. E. Single molecule force spectroscopy on polysaccharides by atomic force microscopy. Science 1997,275, 1295-1297.
13. Zhang, W. K.; Xu, Q. B.; Zou, S.; Li, H. B.; Xu, W. Q.; Zhang, X.; Shao, Z. Z.; Kudera, M.; Gaub, H. B. Single-molecule force spectroscopy on bombyx mori silk fibroin by atomic force microscopy Langmuir 2000,16,4305-4308.
14. Zhang, W. K.; Zhang, X. Single molecule mechanochemistry of macromolecules. Prog. Polym. Sci.2003,28,1271-1295.
15. Zou, S.; Zhang, W. K.; Zhang, X.; Jiang, B. Z. Study on polymer micelles of hydrophobically modified ethyl hydroxyethyl cellulose using single-molecule force spectroscopy. Langmuir 2001,17,4799-4808.
16.王驰,聚丙烯酰胺衍生物的单链拉伸AFM研究,吉林大学硕士学位论文,2003.
17.张文科,单分子纳米力学探测,吉林大学博士学位论文,2002.
18. Cui, S. X.; Liu, C. J.; Zhang, X. Simple method to isolate single polymer chains for the direct measurement of the desorption force. Nano Letters 2003,3,245-248.
19.崔树勋,高分子界面吸附的单分子力谱研究,吉林大学博士学位论文,2004.
20. Evans, E. Energy landscapes of biomolecular adhesion and receptor anchoring at interfaces explored with dynamic force spectroscopy. Faraday Discuss.1998,111, 1-16.
21. Merkel, R.; Nassoy, P.; Leung, A.; Ritchie, K.; Evans, E. Energy landscpes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature 1999, 397,50-53.
22. Morfill, J.; Kuhner, F.; Blank, K.; Lugmaier, R. A.; Sedlmair, J.; Gaub, H. E. B-S transition in short oligonucleotides. Biophysical Journal 2007,93,2400-2409.
23. Dietz, H.; Rief, M. Exploring the energy landscape of GFP by single-molecule mechanical experiments. Proc. Nad. Acad. Sci. U.S.A.2004,101,16192-16197.
24. Best, R. B.; Fowler, S. B.; Toca-Herrera, J. L.; Clarke, J. A simple method for probing the mechanical unfolding pathway of proteins in detail. Proc. Natl. Acad. Sci. U.S.A.2002,99,12143-12148.
25. Evans, E. A.; Calderwood, D. A. Forces and bond dynamics in cell adhesion. Science 2007,316.1148-1153.
26. Bell, G. I. Models for the specific adhesion of cells to cells. Science 1978,200, 618-627.
27. Evans, E.; Ritchie, K. Dynamic strength of molecular adhesion bonds. Biophysical Journal 1997,72,1541-1555.
28. Rief, M.; Clausen-Schaumann, H.; Gaub, H. E. Sequence-dependent mechanics of single DNA molecules. Nat. Struct. Biol.1999,6,346-349.
29. Clausen-Schaumann, H.; Rief, M.; Tolksdorf, C.; Gaub, H. E. Mechanical stability of single DNA molecules. Biophys. J.2000,78,1997-2007.
30. Krautbauer, R.; Fischerlander, S.; Allen, S.; Gaub, H. E. Mechanical fingerprints of DNA drug complexes. Single Mol.2002,3,97-103.
31. Krautbauera, R.; Popeb, L. H.; Schradera, T. E.; Allenb, S.; Gaub, H. E. Discriminating small molecule DNA binding modes by single molecule force spectroscopy. FEBS Letters 2002,510,154-158.
32. Zhang, W. K.; Machon, C.; Orta, A.; Phillips, N.; Roberts, C. J.; Allen, S.; Soultanas, P. Single-molecule atomic force spectroscopy reveals that DnaD forms scaffolds and enhances duplex melting. J. Mol. Biol.2008,377,706-714.
33. Krasnoslobodtsev, A. V.; Shlyakhtenko, L. S.; Lyubchenko, Y. L. Probing interactions within the synaptic DNA-Sfil complex by AFM force spectroscopy. J. Mol. Biol.2007,365,1407-1416.
34. Kuhner, F.; Costa, L. T.; Bisch, P. M.; Thalhammer, S.; Heckl, W. M.; Gaub, H. E. LexA-DNA bond strength by single molecule force spectroscopy. Biophysical Journal 2004,87,2683-2690.
35. Wollschlager, K.; Gaus, K.; Kornig, A.; Eckel, R.; Wilking, S.-D.; Mclntosh, M.; Majer, Z.; Becker, A.; Ros, R.; Anselmetti, D.; Sewald, N. Single-molecule experiments to elucidate the minimal requirement for DNA recognition by transeription factor epitopes. Small 2009,5,484-495.
36. Rief, M.; Gautel, M.; Oesterhelt, F.; Fernandez, J. M.; Gaub, H. E, Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 1997, 276,1109-1112.
37. Marszalek, P. E.; Lu, H.; Li, H. B.; Carrion-Vazquez, M.; Oberhauser, A. F.; Schulten, K.; Fernandez, J. M. Mechanical unfolding intermediates in titin modules. Nature 1999,402,100-103.
38. Oberhauser, A. F.; Marszalek, P. E.; Carrion-Vazquez, M.; Fernandez, J. M. Single protein misfolding events captured by atomic force microscopy. Nat. Struct. Biol.1999,6,1025-1028.
39. Carrion-Vazquez, M.; Marszalek, P. E.; Oberhauser, A. F.; Fernandez, J. M. Atomic force microscopy captures length phenotypes in single proteins. Proc Natl. Acad. Sci. U.S.A.1999,96,11288-11292.
40. Carrion-Vazquez, M.; Oberhauser, A. F.; Fowler, S. B.; Marszalek, P. E.; Broedel, S. E.; Clarke, J.; Fernandez, J. M. Mechanical and chemical unfolding of a single protein:a comparison. Proc. Natl. Acad. Sci. U.S.A.1999,96,3694-3699.
41. Yang, G. L.; Cecconi, C.; Baase, W. A.; Vetter, I. R.; Breyer, W. A.; Haack, J. A.; Matthews, B. W.; Dahlquist, F. W.; Bustamante, C. Solid-state synthesis and mechanical unfolding of polymers of T4 lysozyme. Proc. Natl. Acad. Sci. U.S.A. 2000,97,139-144.
42. Dietz, H.; Rief, M. Exploring the energy landscape of GFP by single-molecule mechanical experiments. Proc. Natl. Acad. Sci. U.S.A.2004,101,16192-16197.
43. Puchner, E. M.; Gaub, H. E. Exploring the conformation-regulated function of titin kinase by mechanical pump and probe experiments with single molecules. Angew. Chem. Int. Ed.2010,49,1-5.
44. Brockwell, D. J.; Paci, E.; Zinober, R. C.; Beddard, G. S.; Olmsted, P. D.; Smith, D. A.; Perham, R. N.; Radford, S. E. Pulling geometry defnes the mechanical resistance of a beta-sheet protein. Nature Struct. Biol.2003,10,731-737.
45. Carrion-Vazquez, M.; Li, H. B.; Lu, H.; Marszalek, P. E.; Oberhauser, A. F. Fernandez, J. M. The mechanical stability of ubiquitin is linkage dependent. Nature Struct. Biol.2003,10,738-743.
46. Dietz, H.; Berkemeier, F.; Bertz, M.; Rief, M. Anisotropic deformation response of single protein molecules. Proc. Natl. Acad. Sci. U.S.A.2006,103, 12724-12728.
47. Oesterhelt, F.; Oesterhelt, D.; Pfeiffer, M.; Engel, A.; Gaub, H. E.; Muller, D. J. Unfolding pathways of individual bacteriorhodopsins. Science 2000,288, 143-146.
48. Kedrov, A.; Janovjak, H.; Sapra, K. T.; Muller, D. J. Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy. Annu. Rev. Biophys. Biomol. Struct.2007,36,233-260.
49. Kedrov, A.; Krieg, M.; Ziegler, C.; Kuhlbrandt, W.; Muller, D. J. Locating ligand binding and activation of a single antiporter. EMBO reports 2005,6,668-674.
50. Kedrov, A.; Ziegler, C.; Muller, D. J. Differentiating ligand and inhibitor interactions of a single antiporter. J. Mol. Biol.2006,362,925-932.
51. Kedrov, A.; Appel, M.; Baumann, H.; Ziegler, C.; Muller, D. J. Examining the dynamic energy landscape of an antiporter upon inhibitor binding. J. Mol. Biol. 2008,375,1258-1266.
52. Rief, M.; Oesterhelt, F.; Heymann, B.; Gaub, H. E. Single molecule force spectroscopy on polysaccharides by atomic force microscopy. Science 1997,275, 1295-1297.
53. Marszalek, P. E.; Oberhauser, A. F.; Pang, Y. P.; Pernandez, J. M. Polysaccharide elasticity governed by chair-boat transitions of glucopyranose ring. Nature 1998, 396,661-664.
54. Marszalek, P. E.; Pang, Y. P.; Li, H. B.; Yazal, J. E.; Oberhauser, A. F.; Pernandez, J. M. Atomic levers control pyranose ring conformations. Proc. Natl. Acad. Sci. U.S.A.1999,96,7894-7898.
55. Li, H. B.; Rief, M.; Oesterhelt, F.; Gaub, H. E.; Zhang, X.; Shen, J. C. Single-molecule force spectroscopy on polysaccharides by AFM:nanomechanical fingerprint of α-(1,4)-linked polysaccharides. Chem. Phys. Lett.1999,305, 197-201.
56. Xu, Q. B.; Zhang, W. K.; Zhang, X. Oxygen bridge inhibits conformational transition of 1,4-linked a-D-galactose detected by single-molecule atomic force microscopy. Macromolecules 2002,35,871-876.
57. Florin, E.-L.; Moy, V. T.; Gaub, H. E. Adhesion forces between individual ligand-receptor pairs. Science 1994,264,415-417.
58. Florin, E.-L.; Gaub, H. E. Intermolecular forces and energies between ligands and receptors. Science 1994,266,257-259.
59. Allen, S.; Chen, X. Y.; Davies, J.; Davies, M. C.; Dawkes, A. C.; Edwards, J. C.; Roberts, C. J.; Sefton, J.; Tendler, S. J. B.; Williams, P. M. Detection of antigen-antibody binding events with the atomic force microscope. Biochemistry 1997,36,7457-7463.
60. Hinterdorfer, P.; Baumgartner, W.; Gruber, H. J.; Schilcher, K.; Schindler, H. Detection and localization of individual antibody-antigen recognition events by atomic force microscopy. Proc. Natl. Acad. Sci. U.S.A.1996,93,3477-3481.
61. Morfill, J.; Neumann, J.; Blank, K.; Steinbach, U.; Puchner, E. M.; Gottschalk, K.-E.; Gaub. H. E. Force-based analysis of multidimensional energy landscapes: application of dynamic force spectroscopy and steered molecular dynamics simulations to an antibody fragment-peptide complex. J. Mol. Biol.2008,381, 1253-1266.
62. Benoit, M.; Gabriel, D.; Gerisch, G.; Gaub, H. E. Discrete interactions in cell adhesion measured by single-molecule force spectroscopy. Nature Cell Biology 2000,2,313-317.
63. Wojcikiewicz, E. P.; Abdulreda, M. H.; Zhang, X. H.; Moy, V. T. Force spectroscopy of LFA-1 and its ligands, ICAM-1 and ICAM-2. Biomacromolecules 2006,7,3188-3195.
64. Krieg, M.; Arboleda-Estudillo, Y.; Puech, P. H.; Kafer, J.; Graner, F.; Muller, D. J.; Heisenberg, C. P. Tensile forces govern germ-layer organization in zebrafish. Nature Cell Biology 2008,10,429-436.
65. Dupres, V.; Alsteens, D.; Andre, G.; Verbelen, C.; Dufrene, Y. F. Fishing single molecules on live cells. Nano Today 2009,4,262-268.
66. Alsteens, D.; Dupres, V.; Me Evoy, K.; Wildling, L.; Gruber, H. J; Dufrene, Y. F. Structure, cell wall elasticity and polysaccharide properties of living yeast cells, as probed by AFM. Nanotechnology 2008,19,384005(1-9).
67. Verbelen, C.; Dufrene, Y. F. Direct measurement of Mycobacterium-fibronectin interactions. Integr. Biol.2009,1,296-300.
68. Alsteens, D.; Dupres, V.; Klotz, S. A.; Gaur, N. K.; Lipke, P. N.; Dufrene, Y. F. Unfolding individual Als5p adhesion proteins on live cells. ACS Nano 2009,3, 1677-1682.
69. Rangl, M.; Nevo, R.; Liashkovich, I.; Shahin, V.; Reich, Z.; Ebner, A.; Hinterdorfer, P. Stable, non-destructive immobilization of native nuclear membranes to micro-structured PDMS for single-molecule force spectroscopy. ChemPhysChem 2009,10,1553-1558.
1. Krautbauera, R.; Popeb, L. H.; Schradera, T. E.; Allenb, S.; Gaub, H. E. Discriminating small molecule DNA binding modes by single molecule force spectroscopy. FEBS Letters 2002,510,154-158.
2. Williams, M. C.; Wenner, J. R.; Rouzina, I.; Bloomfield, V. A. Effect of pH on the overstretching transition of double-stranded DNA:Evidence of force-induced DNA melting. Biophys. J.2001,80,874-881.
3. Rouzina, I.; Bloomfield, V. A. Force-induced melting of the DNA double helix 1. Thermodynamic analysis. Biophys. J.2001,80,882-893.
4. Williams, M. C;. Rouzina, I.; Bloomfield, V. A. Thermodynamics of DNA interactions from single molecule stretching experiments. Ace. Chem. Res.2002, 35,159-166.
5. (a) McCauley, M. J.; Williams, M. C. Mechanisms of DNA binding determinded in optical tweezers experiments. Biopolymers 2007,85,154-168. (b) Shokri, L. Rouzina, I.; Williams, M. C. Interaction of bacteriophage T4 and T7 single-stranded DNA-binding proteins with DNA. Phys. Biol.2009,6, 025002(1-11). (c) Shokri, L.; Marintcheva, B.; Eldib, M.; Hanke, A.; Rouzina, I.; Williams, M. C. Kinetics and thermodynamics of salt-dependent T7 gene 2.5 protein binding to single- and double-stranded DNA. Nucl. Acids Res.2008,36, 5668-5677. (d) Shokri, L.; Marintcheva, B.; Richardson, C. C.; Rouzina, I.; Williams, M. C. Single molecule force spectroscopy of salt-dependent bacteriophage T7 gene 2.5 protein binding to single-strand DNA. J. Biol. Chem. 2006,281,38689-38696. (e) Pant, K.; Karpel, R. L.; Rouzina, I.; Williams, M. C. Salt dependent binding of T4 gene 32 protein to single and double-stranded DNA: single molecule force spectroscopy measurements. J. Mol. Biol.2005,349, 317-330. (f) Pant, K.; Karpel, R. L.; Rouzina, I.; Williams, M. C. Mechanical measurement of single-molecule binding rates:kinetics of DNA helix-destabilization by T4 gene 32 protein. J. Mol. Biol.2004,336,851-870. (g) Pant, K.; Karpel, R. L.; Williams, M. C. Kinetic regulation of single DNA molecule denaturation by T4 gene 32 protein structural domains. J. Mol. Biol.2003,327, 571-578. (h) Shokri, L.; McCauley, M. J.; Rouzina, I.; Williams, M. C. DNA overstretching in the presence of glyoxal:structural evidence of force-induced DNA melting. Biophys. J.2008,95,1248-1255.
6. Rief, M.; Clausen-Schaumann, H.; Gaub, H. E. Sequence-dependent mechanics of single DNA molecules. Nat. Struct. Biol.1999,6,346-349.
7. Clausen-Schaumann, H.; Rief, M.; Tolksdorf, C.; Gaub, H. E. Mechanical stability of single DNA molecules. Biophys. J.2000,78,1997-2007.
8. Ouzel, P.; Lebrun, A.; Heller, C.; Lavery, R.; Viovy, J.-L.; Chatenay, D.; Caron, F. DNA:an extensible molecule. Science 1996,271,792-794.
9. Smith, S. B.; Cui, Y. J.; Bustamante, C. Overstretching B-DNA:the elastic response of individual double-stranded and single-stranded DNA molecules. Science 1996,271,795-799.
10. Cocco, S.; Yan, J.; Leger, J.-F.; Chatenay, D.; Marko, J. F. Overstretching and force-driven strand separation of double-helix DNA. Phys. Rev. E 2004,70, 011910(1-18).
11. Zhou, H. J.; Zhang, Y.; Ou-Yang, Z. Bending and base-stacking interactions in double-stranded DNA. Phys. Rev. Lett.1999,82,4560-4563.
12. Chiang, K. N.; Yuan, C. A.; Han, C. N.; Chou, C. Y.; Cui, Y. J. Mechanical characteristic of ssDNA/dsDNA molecule under external loading. Appl. Phys. Lett.2006,88,023902(1-3).
13. Lebrun, A.; Lavery, R. Modelling extreme stretching of DNA. Nucleic Acids Res. 1996,24,2260-2267.
14. Zhang, W. K.; Dillingham, M. S.; Thomas, C.D.; Allen, S.; Roberts, C. J.; Soultanas, P. Directional loading and stimulation of PcrA helicase by the replication initiator protein RepD. J. Mol. Biol.2007,371,336-348.
15. Zhang,W. K.; Machon, C.; Orta, A.; Phillips, N.; Roberts, C. J.; Allen, S.; Soultanas, P. Single-molecule atomic force spectroscopy reveals that DnaD forms scaffolds and enhances duplex melting. J. Mol. Biol.2008,377,706-714.
16. Zhang, W. K.; Barbagallo, R.; Madden, C.; Roberts, C. J.; Woolford, A.; Allen, S. Progressing single biomolecule force spectroscopy measurements for the screening of DNA binding agents. Nanotechnology 2005,16,2325-2333.
17. Cubeddu, L.; White, M. F. DNA damage detection by an archaeal single-stranded DNA-binding protein. J. Mol. Biol.2005,353,507-516.
18. Bujalowski, W.; Lohman, T. M. Escherichia coli single-strand binding protein forms multiple, distinct complexes with single-stranded DNA. Biochemistry 1986, 25,7799-7802.
19. Kozlov, A. G.; Lohman, T. M. Stopped-flow studies of the kinetics of single-stranded DNA binding and wrapping around the Escherichia coli SSB tetramer. Biochemistry 2002,41,6032-6044.
20. Raghunathan, S.; Kozlov, A. G.; Lohman, T. M.; Waksman, G. Structure of the DNA binding domain of E. coli SSB bound to ssDNA. Nat. Struct. Biol.2000,7, 648-652.
21. Hatch, K.; Danilowicz, C.; Coljee, V.; Prentiss, M. Measurement of the salt-dependent stabilization of partially open DNA by Escherichia coli SSB protein. Nucleic Acids Res.2008,36,294-299.
22. Krautbauer, R.; Fischerlander, S.; Allen, S.; Gaub, H. E. Mechanical fingerprints of DNA drug complexes. Single Mol.2002,3,97-103.
1. Bawden, F. C.; Pirie, N. W.; Bernal, J. D.; Fankuchen, I. Liquid crystalline substances from virus-infected plants. Nature 1936,138,1051-1052.
2. Jonathan, P.; Butler, G. The current picture of the structure and assembly of tobacco mosaic virus. J. gen. Virol.1984,65,253-279.
3. Namba, K.; Stubbs, G. Structure of tobacco mosaic virus at 3.6 A resolution: implications for assembly. Science 1986,231,1401-1406.
4. Stubbs, G. Tobacco mosaic virus particle structure and the initiation of disassembly. Phil. Trans. R. Soc. London, Ser. B 1999,354,551-557.
5. Klug, A. The tobacco mosaic virus particle:structure and assembly. Phil. Trans. R. Soc. London, Ser. B 1999,354,531-535.
6. Sachse, C.; Chen, J. Z.; Coureux, P.-D.; Stroupe, M. E.; Fandrich, M.; Grigorieff, N. High-resolution electron microscopy of helical specimens:a fresh look at tobacco mosaic virus. J. Mol. Biol.2007,371,812-835.
7. Steckert, J. J.; Schuster, T. M. Sequence specificity of trinucleoside diphosphate binding to polymerized tobacco mosaic virus protein. Nature 1982,299,32-36.
8. Shaw, J. G. Tobacco mosaic virus and the study of early events in virus infections. Phil. Trans. R. Soc. London, Ser. B 1999,354,603-611.
9. Niu, Z. W.; Bruckman, M. A.; Li, S. Q.; Lee, A.; Lee, B.; Pingali, S. V.; Thiyagarajan, P.; Wang, Q. Assembly of tobacco mosaic virus into fibrous and macroscopic bundled arrays mediated by surface aniline polymerization. Langmuir 2007,23,6719-6724.
10. Royston, E.; Ghosh, A.; Kofinas, P.; Harris, M. T.; Culver, J. N. Self-assembly of virus-structured high surface area nanomaterials and their application as battery electrodes. Langmuir 2008,24,906-912.
11. Peng, B.; Liu, N. N.; Lin, Y.; Wang, L. M.; Zhang, W. K.; Niu, Z. W.; Wang, Q.; Su, Z. H. Self-assembly of anisotropic tobacco mosaic virus nanoparticles on gold substrate. Sci China Chem.2011,54,137-143.
12. Zhang, W. K.; Zhang, X. Single molecule mechanochemistry of macromolecules. Prog. Polym. Sci.2003,28,1271-1295.
13. Rief, M.; Clausen-Schaumann, H.; Gaub, H. E. Sequence-dependent mechanics of single DNA molecules. Nat. Struct. Biol.1999,6,346-349.
14. Cui, S. X.; Yu, J.; Kiihner, F.; Schulten, K.; Gaub, H. E. Double-stranded DNA dissociates into single strands when dragged into a poor solvent. J. Am. Chem. Soc.2007,129,14710-14716.
15. Smith, S. B.; Cui, Y. J.; Bustamante, C. Overstretching B-DNA:the elastic response of individual double-stranded and single-stranded DNA molecules. Science 1996,271,795-799.
16. Valle, F.; Zuccheri, G.; Bergia, A.; Ayres, L.; Rowan, A. E.; Nolte, R. J. M.; Samori, B. A polymeric molecular "handle" for multiple AFM-based single-molecule force measurements. Angew. Chem., Int. Ed.2008,47, 2431-2434.
17. Morfill, J.; Kuhner, F.; Blank, K.; Lugmaier, R. A.; Sedlmair, J.; Gaub, H. E. B-S Transition in Short Oligonucleotides. Biophysical Journal 2007,93,2400-2409.
18. Dietz, H.; Rief, M. Exploring the energy landscape of GFP by single-molecule mechanical experiments. Proc. Natl. Acad. Sci. U.S.A.2004,101,16192-16197.
19. Best, R. B.; Fowler, S. B.; Toca-Herrera, J. L.; Clarke, J. A simple method for probing the mechanical unfolding pathway of proteins in detail. Proc. Natl. Acad. Sci. U.S.A.2002,99,12143-12148.
20. Evans, E. Energy landscapes of biomolecular adhesion and receptor anchoring at interfaces explored with dynamic force spectroscopy. Faraday Discuss.1998,111, 1-16.
21. Merkel, R.; Nassoy, P.; Leung, A.; Ritchie, K.; Evans, E. Energy landscapes of receptor-ligand bonds explored with dynamic force spectroscopy. Nature 1999, 397,50-53.
22. Zhang, W. K.; Zhang, X. Single molecule mechanochemistry of macromolecules. Prog. Polym. Sci.2003,28,1271-1295.
23. Namba, K.; Pattanayek, R.; Stubbs, G. Visualization of protein-nucleic acid interactions in a virus refined structure of intact tobacco mosaic virus at 2.9 A resolution by X-ray fiber diffraction. J. Mol. Biol.1989,208,307-325.
1. Steckert, J. J.; Schuster, T. M. Sequence specificity of trinucleoside diphosphate binding to polymerized tobacco mosaic virus protein. Nature 1982,299,32-36.
2. Bell, G. I. Models for the specific adhesion of cells to cells. Science 1978,200, 618-627.
3. Evans, E.; Ritchie, K. Dynamic strength of molecular adhesion bonds. Biophysical Journal 1997,72,1541-1555.
4. Niu, Z. W.; Bruckman, M. A.; Li, S. Q.; Lee, A.; Lee, B.; Pingali, S. V.; Thiyagarajan, P.; Wang, Q. Assembly of tobacco mosaic virus into fibrous and macroscopic bundled arrays mediated by surface aniline polymerization. Langmuir 2007,23,6719-6724.
5. Peng, B.; Liu, N. N.; Lin, Y.; Wang, L. M.; Zhang, W. K.; Niu, Z. W.; Wang, Q.; Su, Z. H. Self-assembly of anisotropic tobacco mosaic virus nanoparticles on gold substrate.Sci China Chem.2011,54,137-143.
6. Rief, M.; Fernandez, J. M.; Gaub, H. E. Elastically coupled two-level systems as a model for biopolymer extensibility. Phys. Rev. Lett.1998,81,4764-4767.
7. Jonathan, P.; Butler, G. The current picture of the structure and assembly of tobacco mosaic virus. J. gen. Virol.1984,65,253-279.
8. Namba, K.; Pattanayek, R.; Stubbs, G. Visualization of protein-nucleic acid interactions in a virus refined structure of intact tobacco mosaic virus at 2.9 A resolution by X-ray fiber diffraction. J. Mol. Biol.1989,208,307-325.
9. Yuan, C. B.; Chen, A.; Kolb, P.; Moy, V. T. Energy landscape of streptavidin-biotin complexes measured by atomic force microscopy. Biochemistry 2000,39, 10219-10223.
10. Piramowicz, M. D.; Czuba, P.; Targosz, M.; Burda, K.; Szymonski, M. Dynamic force measurements of avidin-biotin and streptavidin-biotin interactions using AFM. Acta Biochim. Polon.2006,53,93-100.
11. Bjornham, O.; Nilsson, H.; Andersson, M.; Schedin, S. Physical properties of the specific PapG-galabiose binding in E-coli P pili-mediated adhesion. European Biophysics Journal with Biophysics Letters 2009,38,245-254.
12. Yan, C.; Yersin, A.; Afrin, R.; Sekiguchi, H.; Ikai, A. Single molecular dynamic interactions between glycophorin A and lectin as probed by atomic force microscopy. Biophysical Chemistry 2009,144,72-77.
13. Bloomer, A. C.; Champness, J. N.; Bricogne, G.; Staden, R.; Klug, A. Protein disk of tobacco mosaic virus at 2.8 A resolution showing the interactions within and between subunits. Nature 1978,276,362-368.