• Proteins

    SPM Applications in Biology


    Proteins play a fundamental role in the structure and the vital functions of all living creatures. This wide class of biomolecules includes well-known names such as albumin, hemoglobin and insulin. Atomic Force Microscopy from its very beginning has contributed significantly to understanding the peculiarities of protein functioning and has provided extra information about their structure and properties.

    Atomic Force Microscopy has been successfully employed in exploring protein adsorption onto solid surfaces along with radiolabeling, fluorescence spectroscopy, ellipsometry and other methods. It is quite important in the investigation of implant biocompatibility, in-vitro cell growth, membrane fouling, protein purification and biosensor design. The behavior of proteins at surface defect sites is of interest, as such defects may provide a means of immobilizing biological molecules for detection purposes [1086]. Protein-covered surfaces may be also useful for the catalysis of biological reactions.

    Y. F. Dufrene at al. [677, 1527] investigate the organization of collagen adsorbed onto polymer substrates. Combining XPS and radiolabeling they proposed a quantitative description of the layer on the basis of a simple geometric model. AFM allows to confirm this organization by direct observation of the continuous or discontinuous character of the adsorbed layer and provided novel information by revealing topographic features at supramolecular scale (fibrillar structures).

    A.P. Quist at al. [804] study the adsorption of albumin (HSA) and tripsin molecules on mica surfaces using AFM. The observed hillocks indicate that molecules are adsorbed partly as aggregates and partly as isolated single molecules. A qualitative estimate of the profiles of the adsorbed molecules can be obtained, giving vivid information on the conformation and domain structure of the adsorbed molecules. Individual molecules are resolved. By the opinions of the authors, it is very exciting that the structure and conformation of individual molecules can be observed in tapping mode AFM, making it a powerful tool for biological research.

    P. Kernen at al. [869] investigate aggregations of the largest light-harvesting pigment-protein complex of Photosystem II (SHC II) deposited on glass using the Langmuir-Blodget films technique. The formation of Langmuir-Blodget films with incorporated biomolecules of interest is a common way in preparing flat mono- or multilayer species for measurements with various methods including AFM. Direct observation of the structural organizations in these films helps us to understand specific interactions between molecules within the layer. SHC II is an antenna protein in higher plants comprising almost half of the total pool of the main photosynthetic accessory pigment chlorophylls. Ring-like structures formed in monocomponent protein layers as well as in mixed protein-lipid films were revealed using AFM. It is suggested that LHC II organizes as round-shaped circles with internal diameters of 150 - 250 Å and external diameters of 300 - 500 Å.

    Epand at al. [696] first apply Atomic Force Microscopy to study the properties of the hemagglutinin (HA) protein of influenza virus. Association of two different forms of the ectodomain of this protein at supported lipid bilayer interfaces as a function of pH and incubation time was explored. These are bromelaincleaved hemagglutinin (BHA), corresponding to the full ectodomain of the HA protein, and FHA2, the 127 amino acid N-terminal fragment of the HA2 subunit of the hemagglutinin protein. The results provide direct evidence of different protein aggregation phenomena at model lipid surfaces for the BHA and FHA2 fragments of the influenza HA, that may be relevant to their function. The results presented in this paper are the first example of in situ imaging of the ectodomain of a viral envelope protein allowing characterization of the real-time selfassembly of a membrane fusion protein.

    The nondestructive character of Atomic Force Microscopy and the possibility of operation in nearly any physiological conditions prompted studies of lachrymal deposits on Soft Contact Lens (SCL) that are mainly composed of proteins. J. Baguet at al. [445] suggest that AFM is a new exceptional tool for exploring biomaterials and biomolecular-surface interactions by extending the atomic resolution of the scanning tunnelling microscope to non-conducting materials. The use of Scanning Electron Microcopy in such a case faces several disadvantages since lens preparation affects the structure and the surface of the unworn and worn lenses, some deposits are artefactual and the damaging electron beam causes SCL destruction. For proteins identification the combination of AFM and a sodium dodecil sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of extracted SCL deposits were performed in parallel fashion. Thus, new and unique information on SCL deposits from contacting lachrymal component shows that adsorption on surfaces during continuous wear of the soft contact lenses is a two-step mechanism. First, a uniform coating, probably composed of proteins and mucosubstances, covers the surface. Second, structured deposits appear on the lens surface and quickly form an additional layer over the first protein coating. The images clearly show the evolution of the size and structure of these deposits.

    The growth of proteins from solutions in crystalline form [118] also attracts large attention in the scientific world. In the last years a number of in situ AFM studies have been performed on lysozyme [119, 546, 1087, 1088, 1089], canavalin [235, 597, 759, 1090, 1092], thaumatin [546, 755, 1091, 1092], a-amilase [300], catalase [222]. Studying the processes of macromolecular crystallization helps to understand better growth kinetics and nucleation mechanisms in crystal growth as a whole. For instance, the investigation of the growth behavior of porcine pancreatic a-amylase at defined supersaturation, performed by J.P. Astier at al. [300], reveals that at high supersaturation (b = 1.6) 2-D nucleation is to be the dominating growth mechanism, whereas at lower supersaturation (b = 1.3) the growth process appears to be defect controlled (spiral growth). The analysis of step heights on 2-D nucleation islands (monomolecular protein layers) and growth steps (two molecules in height) in combination with results from light scattering experiments suggests that a single protein molecule is the basic growth unit.

    Although similar or higher resolution can be obtained by electron microscopy and X-ray crystallography, the excellent signal-to-noise ratio of AFM topographs allows the direct imaging of native proteins [309, 522, 1094] and their substructures to a resolution of about 0.5 nm [1099]. AFM enables conformational changes of single proteins and of their assemblies to be observed directly [1501]. Furthermore, conformational changes can be induced in a controlled manner to identify flexible protein structures [1095, 1098, 1505].

    The plasma membrane of the cell comprises diverse membrane proteins, including integral membrane proteins such as receptors, ion channels and transporters, as well as certain antigens that are peripherally associated with the membrane. Because of their important roles in cell growth, differentiation and cell-cell signaling, the structures of the plasma membrane and proteins associated with it have attracted wide attention and have been extensively investigated. During the two decades the study of native membrane proteins evolves from measuring AFM topography of the protein layer to single molecule force spectroscopy [381, 1503, 1505, 1517]. In situ AFM investigations of protein-lipid interactions are also performed [1081]. Continuous progress in the AFM apparatus, measurment technique and sample preparation can be clearly seen for one of the most popular object of protein nature ever imaged with AFM - bacteriorhodopsin (BR) covering the purple membrane (PM). This protein acts as a light driven proton pump to produce a finite difference in the proton concentration between the inside and outside of the cell membrane [256]. As summarized by Müller at al. [381], trimeric BR molecules arrange in a trigonal lattice of 6.2 ± 0.2 nm side length. Power spectra of the observed structure suggest lateral resolution as low as 0.45 nm. Such excellent spatial resolution as well as extrasensitivity at low AFM cantilever loading ranging from 100 nN to 300 nN allows to investigate the major conformations of BR surfaces and to map the variability and the flexibility of individual polypeptide loops connecting transmembrane K-helices of BR. It is revealed that full conformation of the trimer is accomplished when loading force rises from 100 pN to 200 pN. Application of force up to 300 pN results in a deformation of the peripheral protrusions of the trimer and structural information of these areas is lost. Detailed analysis of images obtained allows to differentiate six K-helices of the protein according to their flexibility under load applied. Comparison of AFM data and atomic models of BR (to date six model are offered) derived from electron and X-ray diffraction experiments are presented. There is an excellent correspondence between the surface loops of the BR model and the AFM envelope. Standard deviation maps of the height measured by AFM correspond well with the relative distribution of B-factors of the atomic models as well as the coordinate variance between the models. S.D. maps help revealing the elasticity of single polypeptide loops. In contrast to electron and X-ray crystallography methods, AFM can be used to image surface structures of BR in a buffer solution and at room temperature similar to their physiological environment. All this evidence supports the idea that the AFM not only fulfills the prerequisites to directly monitor function related conformational changes of biological macromolecules [427, 1093, 1502, 1504] but can also characterize dynamic aspects of protein structures, such as their flexibility and variability.

    In single molecule force-spectroscopy experiments, the protein complexes are tethered to both support and AFM tip to measure their cohesion when the AFM tip and the support are moved apart. This technique is employed to measure forces between pairs of interacting biological molecules [789, 790, 794, 795, 797, 1509] and forces required for the unfolding of titin domains [1512]. Protein complexes are imaged before and after the removal of individual subunits using the AFM tip as a dissecting nanotool [1096]. Based on these results, the single molecule imaging and single molecule force-spectroscopy capabilities of the AFM arecombined to provide novel insights into the inter- and intramolecular interactions of proteins [1515, 1516]. Applied to membrane proteins, these combined techniques allow forces to be measured that anchor the protein in the native membrane, as well as forces required to unfold the tertiary and secondary structure of the protein [1516], and the protein to be imaged at subnanometer resolution.

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    ID Reference list (newly come references are marked red)
    118 AFM studies of the nucleation and growth mechanisms of macromolecular crystals
    Y.G. Kuznetsov, A.J. Malkin, A. McPherson
    Journal of Crystal Growth, 196 (1999), 2-4, 489-502
    119 Direct AFM observations of impurity effects on a lysozyme crystal
    G. Sazaki, S.D. Durbin, S. Miyashita, H. Komatsu, T. Nakada
    Journal of Crystal Growth, 196 (1999), 2-4, 503-510
    222 An in situ AFM investigation of catalase crystallization
    Y.G. Kuznetsov, A.J. Malkin, A. McPherson
    Surface Science, 393 (1997), 1-3, 95-107
    235 An in-situ AFM investigation of canavalin crystallization kinetics
    T.A. Land, J.J. De Yoreo, J.D. Lee
    Surface Science, 384 (1997), 1-3, 136-155
    256 STM and AFM of bio/organic molecules and structures
    A. Ikai
    Surface Science Reports, 26 (1997), 261-332
    300 a-amylase crystal growth investigated by in situ atomic force microscopy
    J.P. Astier, D. Bokern, L. Lapena, S. Veesler
    Journal of Crystal Growth, 226 (2001), 2-3, 294-302
    306 Adsorption of proteins to fused-silica capillaries as probed by atomic force microscopy
    J.J. Bonvent, R. Barberi, R. Bartolino, L. Capelli, P.G. Righetti
    Journal of Chromatography A, 756 (1996), 1-2, 233-243
    309 An atomic force microscopy investigation of protein crystal surface topography
    Valeria Mollica, Alberto Borassi, Annalisa Relini, Ornella Cavalleri, Martino Bolognesi, Ranieri Rolandi, Alessandra Gliozzi
    European Biophysics Journal, 30 (2001), 5, 313-318
    381 Atomic force microscopy of native purple membrane
    D.J. Müller, J.B. Heymann, F. Oesterhelt, C. Möller, H. Gaub, G. Büldt, A. Engel
    Biochimica et Biophysica Acta (BBA)/Bioenergetics, 1460 (2000), 1, 27-38
    427 Atomic force microscopy: a powerful tool to observe biomolecules at work
    A. Engel, Y. Lyubchenko, D.J. Müller
    Trends Cell Biol. 9 (1999) 77-80
    445 Characterization of lacrymal component accumulation on worn soft contact lens surfaces by atomic force microscopy
    J. Baguet, F. Sommer, V. Claudon-Eyl, T.M. Duc
    Biomaterials, 16 (1995), 1, 3-9
    522 High resolution surface structure of Escherichia coliGroES oligomer by atomic force microscopy
    M. Jianxun, D.M. Czajkowsky, S. Sitong, H. Rouya, S. Zhifeng
    FEBS Letters, 381 (1996), 1-2, 161-164
    546 In situ atomic force microscopy studies of surface morphology, growth kinetics, defect structure and dissolution in macromolecular crystallization
    A.J. Malkin, A. McPherson, Y.G. Kuznetsov
    Journal of Crystal Growth, 196 (1999), 2-4, 471-488
    597 Mechanisms of protein and virus crystal growth: An atomic force microscopy study of canavalin and STMV crystallization
    T.A. Land, J.J. De Yoreo, A.J. Malkin, Y.G. Kutznesov, A. McPherson
    Journal of Crystal Growth, 166 (1996), 1-4, 893-899
    677 Probing the organization of adsorbed protein layers: complementarity of atomic force microscopy, X-ray photoelectron spectroscopy and radiolabeling
    Y.F. Dufrene, T.G. Marchal, P.G. Rouxhet
    Applied Surface Science, 144-145 (1999), 638-643
    696 Self-assembly of influenza hemagglutinin: studies of ectodomain aggregation by in situ atomic force microscopy
    R.F. Epand, C.M. Yip, L.V. Chernomordik, D.L. LeDuc, Y.-K. Shin, R.M. Epand
    Biochimica et Biophysica Acta (BBA)/Biomembranes, 1513 (2001), 2, 167-175
    755 The advancement and structure of growth steps on thaumatin crystals visualized by atomic force microscopy at molecular resolution
    A. McPherson, Y.G. Kuznetsov, A.J. Malkin, J. Konnert
    Surface Science, 440 (1999), 1-2, 69-80
    759 The evolution of growth modes and activity of growth sources on canavalin investigated by in situ atomic force microscopy
    J.J. De Yoreo, T.A. Land
    Journal of Crystal Growth, 208 (2000), 1-4, 623-637
    789 Sensing Discrete Streptavidin-Biotin Interactions with Atomic Force Microscopy
    G.U. Lee, D.A. Kidwell, R.J. Colton
    Langmuir 10 (1994) 354-357
    790 Direct measurement of the forces between complementary strands of DNA
    G.U. Lee, L.A. Chrisey, R.J. Colton
    Science 266 (1994) 771-773
    794 Adhesion forces between individual ligand-receptor pairs
    E.-L. Florin, V.T. Moy, H.E. Gaub
    Science 264 (1994) 415- 417
    795 Binding strength between cell adhesion proteoglycans measured by atomic force microscopy
    U. Dammer, O. Popescu, P. Wagner, D. Anselmetti, H.J. Guntherodt, G.N. Misevic
    Science 267 (1995) 1173-1175
    797 Specific antigen/antibody interactions measured by force microscopy
    U. Dammer, M. Hegner, D. Anselmetti, P. Wagner, M. Dreier, W. Huber, H.J. Guntherodt
    Biophys. J. 70 (1996) 2437-2441
    804 A scanning force microscopy study of human serum albumin and porcine pancreas trypsin adsorption on mica surfaces
    A.P. Quist, C.T. Reimann, B.U.R. Sundqvist, L.P. Bjorck, S.O. Oscarsson
    Surface Science, 325 (1995), 1-2, l406-l412
    869 Light-harvesting complex II in monocomponent and mixed lipid-protein monolayers
    Z. Krupa, M. Matula, P. Kernen, U. Ziegler, W.I. Gruszecki, P. Wagner
    Biochimica et Biophysica Acta (BBA)/Biomembranes, 1373 (1998), 2, 289-298
    1081 a-Synuclein Membrane Interactions and Lipid Specificity
    E. Jo, J. McLaurin, C.M. Yip, P. George-Hyslop, P.E. Fraser
    J. Biol. Chem. 275 (2000) 34328-34334
    1082 Review: Modulating Factors in Amyloid-Fibril Formation
    J. McLaurin, D. Yang, C.M. Yip, P.E. Fraser
    J. Struct. Biol. 130 (2000) 259-270
    1083 The Heptameric Prepore of a Staphylococcal alpha-Hemolysin Mutant in Lipid Bilayers Imaged by Atomic Force Microscopy
    Y. Fang, S. Cheley, H. Bayley, J. Yang
    Biochemistry 36 (1997), 9518-9522
    1084 New Approach for Atomic Force Microscopy of Membrane Proteins The Imaging of Cholera Toxin
    J. Yang, L.K. Tamm, T.W. Tillack, Z. Shao
    J. Mol. Biol. 229 (1993) 286-290
    1085 Gramicidin A Aggregation in Supported Gel State Phosphatidylcholine Bilayers
    J. Mou, D.M. Czajkowsky, Z. Shao
    Biochemistry 35 (1996) 3222-3226
    1086 Scanning tunneling microscopy studies of carbon-oxygen reactions on highly oriented pyrolytic graphite
    H.Chang and A.J. Bard
    J. Am. Chem. Soc. 113 (1991) 5588
    1087 Lysozyme crystal growth studied by atomic force microscopy
    S.D. Durbin, W.E. Carlson
    J. Crystal Growth 122 (1992) 71
    1088 In situ studies of protein crystal growth by atomic force microscopy
    S.D. Durbin, W.E. Carlson, M.T. Saros
    J. Phys. D: Appl. Phys. 26 (1993) B128
    1089 Observation of growth steps, spiral dislocations and molecular packing on the surface of lysozyme crystals with the atomic force microscope
    J.H. Konnert, P. dAntonio, K.B. Ward
    Acta Crystallogr. D 50 (1994) 603
    1090 Mechanisms of Protein Crystal Growth: An Atomic Force Microscopy Study of Canavalin Crystallization
    T.A. Land, A.J. Malkin, Yu.G. Kuznetsov, A. McPherson, J.J. De Yoreo
    Phys. Rev. Lett. 75 (14) (1995) 2774
    1091 Atomic Force Microscopy Studies of Surface Morphology and Growth Kinetics in Thaumatin Crystallization
    A.J. Malkin, Yu.G. Kuznetsov,W. Glantz, A. McPherson
    J. Phys. Chem. 100 (1996) 11736
    1092 Defect Structure of Macromolecular Crystals
    A.J. Malkin, Yu.G. Kuznetsov, A. McPherson
    J. Struct. Biol. 117 (1996) 124
    1093 Imaging crystals, polymers, and processes in water with the atomic force microscope
    B. Drake, C.B. Prater, A.L. Weisenhorn, S.A.C. Gould, T.R. Albrecht, C.F. Quate, D.S. Cannell, H.G. Hansma, P.K. Hansma
    Science 243 (1989) 1586-1588
    1094 Native Escherichia coliOmpF porin surfaces probed by atomic force microscopy
    F.A. Schabert, C. Henn, A. Engel
    Science 268 (1995) 92-94
    1096 Surface Analysis of the Photosystem I Complex by Electron and Atomic Force Microscopy
    D. Fotiadis, D.J. Müller, G. Tsiotis, L. Hasler, P. Tittmann, T. Mini, P. Jeno, H. Gross, A. Engel
    J. Mol. Biol. 283 (1998) 83-94
    1097 Staphylococcal a-Hemolysin Can Form Hexamers in Phospholipid Bilayers
    D.M. Czajkowsky, S. Sheng, Z. Shao
    J. Mol. Biol. 276 (1998) 325-330
    1098 High resolution AFM topographs of the Escherichia coliwater channel aquaporin Z
    S. Scheuring, P. Ringler, M. Borgina, H. Stahlberg, D.J. Müller, P. Agre, A. Engel
    EMBO J. 18 (1999) 4981-4987
    1099 Electrostatically Balanced Subnanometer Imaging of Biological Specimens by Atomic Force Microscope
    D.J. Müller, D. Fotiadis, S. Scheuring, S.A. Müller, A. Engel
    Biophys. J. 76 (1999) 1101-1111
    1500 Mapping flexible protein domains at subnanometer resolution with the atomic force microscope
    D.J. Müller, D. Fotiadis, A. Engel
    FEBS Lett. 430 (1998) 105-111
    1501 Conformational change of the hexagonally packed intermediate layer of Deinococcus radioduransmonitored by atomic force microscopy
    D.J. Müller, W. Baumeister, A. Engel
    J. Bacteriol. 178 (1996) 3025-3030
    1502 Structural Changes in Native Membrane Proteins Monitored at Subnanometer Resolution with the Atomic Force Microscope: A Review
    D.J. Müller, C.-A. Schoenenberger, F. Schabert, A. Engel
    J. Struct. Biol. 119 (1997) 149-157
    1503 Surface Structures of Native Bacteriorhodopsin Depend on the Molecular Packing Arrangement in the Membrane
    D.J. Müller, H.-J. Sass, S. Müller, G. Büldt, A. Engel
    J. Mol. Biol. 285 (1999) 1903-1909
    1504 Voltage and pH-induced Channel Closure of Porin OmpF Visualized by Atomic Force Microscopy
    D.J. Müller, A. Engel
    J. Mol. Biol. 285 (1999) 1347-1351
    1505 Force-induced Conformational Change of Bacteriorhodopsin
    D.J. Müller, G. Büldt, A. Engel
    J. Mol. Biol. 249 (1995) 239-243
    1509 Adhesive forces between ligand and receptor measured by AFM
    V.T. Moy, E.-L. Florin, H.E. Gaub
    Coll. Surf. A93 (1994) 343-348
    1512 Reversible unfolding of individual titin Ig-domains by AFM
    M. Rief, M. Gautel, F. Oesterhelt, J.M. Fernandez, H.E. Gaub
    Science 276 (1997) 1109-1112
    1513 The molecular elasticity of the extracellular matrix protein tenascin
    A.F. Oberhauser, P.E. Marszalek, H.P. Erickson, J.M. Fernandez
    Nature 393 (1998) 181-185
    1514 Mechanical and chemical unfolding of a single protein: A comparison
    M. Carrion-Vazquez, A.F. Oberhauser, S.B. Fowler, P.E. Marszalek, S.E. Broedel, J. Clarke, J.M. Fernandez
    Proc. Natl. Acad. Sci. USA 96 (1999) 3694-3699
    1515 Controlled unzipping of a bacterial surface layer with atomic force microscopy
    D.J. Müller, W. Baumeister, A. Engel
    Proc. Natl. Acad. Sci. USA 96 (1999) 13170-13174
    1516 Unfolding pathways of individual bacteriorhodopsins
    F. Oesterhelt, D. Oesterhelt, M. Pfeiffer, A. Engel, H. Gaub, D.J. Müller
    Science 288 (2000) 143-146
    1517 Atomic force microscopy of purple membranes
    D.L. Worcester, R.G. Miller, P.J. Bryant
    J. Microsc. 152 (1988) 817-821
    1518 Imaging bacteriorhodopsin lattices in purple membranes with atomic force microscopy
    D.L. Worcester, H.S. Kim, R.G. Miller, P.J. Bryant
    J. Vac. Sci. Technol. A8 (1990) 403-405
    1519 Imaging the membrane protein bacteriorhodopsin with the atomic force microscope
    H.-J. Butt, K.H. Downing, P.K. Hansma
    Biophys. J. 58 (1990) 1473-1480
    1520 Imaging purple membranes dry and in water with the atomic force microscope
    H.-J. Butt, C.B. Prater, P.K. Hansma
    J. Vac. Sci. Technol. B9 (1991) 1193-1197
    1521 Quantitative scanning tunneling and scanning force microscopy of organic materials
    H.-J. Butt, R. Guckenberger, J.P. Rabe
    Ultramicroscopy 46 (1992) 375-393
    1522 Imaging purple membranes in aqueous solutions at sub-nanometer resolution by atomic force microscopy
    D.J. Müller, F.A. Schabert, G. Büldt, A. Engel
    Biophys. J. 68 (1995) 1681-1686
    1523 Immuno-atomic force microscopy of purple membrane
    D.J. Müller, C.A. Schoenenberger, G. Büldt, A. Engel
    Biophys. J. 70 (1996) 1796-1802
    1524 Tapping-Mode Atomic Force Microscopy Produces Faithful High-Resolution Images of Protein Surfaces
    C. Möller, M. Allen, V. Elings, A. Engel, D.J. Müller
    Biophys. J. 77 (1999) 1050-1058
    1525 Scanning force microscopy and geometrical analysis of two-dimensional collagen network formation
    M. Mertig, U. Thiele, J. Bradt, G. Leibiger, W. Pompe, H. Wendrock
    Surf. Interface Anal. 25 (1997) 514
    1526 Real-Time Observation of Plasma Protein Film Formation on Well-Defined Surfaces with Scanning Force Microscopy
    T.C. Ta, M.T. Sykes, M.T. McDermott
    Langmuir 14 (1998) 2435
    1527 Collagen adsorption on poly(methyl methacrylate) : net-like structure formation upon drying
    Ch.C. Dupont-Gillain, B. Nysten, P.G. Rouxhet
    Polymer Int., 48, (1999), 271-276
    37 Investigation of polystyrene nanoparticles and DNA-protein complexes by AFM with image reconstruction
    C.F. Zhu, I. Lee, X. Wang, C. Wang, C. Bai
    Applied Surface Science, 126 (1998), 3-4, 281-286
    98 AFM force measurements on microtubule-associated proteins: the projection domain exerts a long-range repulsive force
    R. Mukhopadhyay, J.H. Hoh
    FEBS Letters, 505 (2002), 3, 374-378
    127 In situ STM and AFM of the copper protein Pseudomonas aeruginosa azurin
    E.P. Friis, J.E.T. Andersen, L.L. Madsen, P. Möller, J. Ulstrup
    Journal of Electroanalytical Chemistry, 431 (1997), 1, 35-38
    397 Atomic Force Microscopy Studies on Whey Proteins
    C. Elofsson, P. Dejmek, M. Paulsson, H. Burling
    International Dairy Journal, 7 (1997), 12, 813-819
    481 Dynamics of Pseudomonas aeruginosa azurin and its Cys3Ser mutant at single-crystal gold surfaces investigated by cyclic voltammetry and atomic force microscopy
    E.P. Friis, J.E.T. Andersen, L.L. Madsen, N. Bonander, P. Möller, J. Ulstrup
    Electrochimica Acta, 42 (1997), 19, 2889-2897
    540 Immunogold Localisation of P-glycoprotein in Supported Lipid Bilayers by Transmission Electron Microscopy and Atomic Force Microscopy
    I. Ruspantini, M. Diociaiuti, R. Ippoliti, E. Lendaro, M. C. Gaudiano, M. Cianfriglia, P. Chistolini, G. Arancia, A. Molinari
    Histochemical Journal, 33 (2001), 5, 305-309
    545 In situ atomic force microscopy studies of protein and virus crystal growth mechanisms
    A.J. Malkin, Y.G. Kuznetsov, W. Glantz, A. McPherson
    Journal of Crystal Growth, 168 (1996), 1-4, 63-73
    791 Effects of Discrete Protein-Surface Interactions in Scanning Force Microscopy Adhesion Force Measurements
    Stuart J.K. and Hlady V.
    Langmuir 11 (1995), 1368-1374
    796 Detection and localization of individual antibody-antigen recognition events by atomic force microscopy
    Hinterdorfer P., Baumgartner W., Gruber H.J., Schilcher K. and Schindler H.
    Proc. Natl. Acad. Sci. USA 93 (1996), 3477-3481
    949 The role of pulmonary surfactant protein C during the breathing cycle
    H.-J. Galla, M. Sieber, M. Amrein, A. Von Nahmen, N. Bourdos
    Thin Solid Films, 327-329 (1998), 632-635
    964 Cell-surface receptors and proteins on platelet membranes imaged by scanning force microscopy using immunogold contrast enhancement
    Eppell S.J., Simmons S.R., Albrecht R.M., Marchant R.E.
    Biophys. J. 68 (1995), 671-680
    967 Structural changes in native membrane proteins monitored at subnanometer resolution with the atomic force microscopy: A review.
    Müller D.J., Schoenenberger C.A., Schabert F., Engel A. J.
    Struct Biol 119 (1997), 149-157
    974 Investigation of the image contrast of tapping-mode atomic force microscopy using protein-modified cantilever tips
    You H.X., Yu L.
    Biophys. J. 73 (1997), 3299-3308
    986 Protein tracking and detection of protein motion using atomic force microscopy
    Thomson N.H., Fritz M., Radmacher M., Cleveland J.P., Schmidt C.F., Hansma P.K.
    Biophys. J. 70 (1996), 2421-2431
    987 Imaging ROMK1 inwardly rectifying ATP-sensitive K+ channel proteins using atomic force microscopy
    Henderson R.M., Schneider S., Li Q., Hornby D., White S.D.I., Oberleithner H.
    Proc. Natl. Acad. Sci. USA 93 (1996), 8756-8760
    1067 Study of dynamics of conformational transitions in membrane-protein complexes by means of scanning probe microscopy in native conditions
    V.I. Lobyshev
    Èíôîðìàoèîííûé áþëëåòåíü ÐÔÔÈ (rus), 4 (1996), 4, 542
    1073 The application of electrochemical scanning probe microscopy to the interpretation of metalloprotein voltammetry
    J.J. Davis, H.A.O. Hill, A.M. Bond
    Coordination Chemistry Reviews, 200-202 (2000), 411 - 442
    1507 Imaging single-stranded DNA, antigen-antibody reaction and polymerized Langmuir-Blodgett films with an AFM
    A.L. Weisenhorn, H.E. Gaub, H.G. Hansma, R.L. Sinsheimer, G.L. Kelderman and P.K. Hansma
    Scanning Microsc. 4 (1990) 511
    1580 Probing protein-protein interactions in real time [In Process Citation]
    Viani M.B., Pietrasanta L.I., Thompson J.B., Chand A., Gebeshuber I.C., Kindt J.H., Richter M., Hansma H.G., Hansma P.K.
    Nat Struct Biol 7 (2000), 8, 644-647
    1335 Surfaces coated with protein layers: a surface force and ESCA study
    E. Blomberg, P. M. Claesson, J. C. Fröberg
    Biomaterials 19 (1998) 371-386
    1355 Conformational changes, flexibilities and intramolecular forces observed on individual proteins using AFM
    Daniel J. Müller and Andreas Engel
    RIKEN Review 36 (2001) 29-31
    1356 From art to science in protein crystallization by means of thin-film nanotechnology
    Eugenia Pechkova and Claudio Nicolini
    Nanotechnology 13 (2002) 460-464
    1369 SPM for Functional Identification of Individual Biomolecules
    R. Ros, F. Schwesinger, C. Padeste, A. Plückthun, D. Anselmetti, Hans-Joachim Güntherodt, and Louis Tiefenauer
    SPIE, 3607 (1999) 84-88
    1397 Reversible stretching of a monomeric unit in a dimeric bovine carbonic anhydrase B with the atomic force microscope
    Tong Wang, Hideo Arakawa and Atsushi Ikai
    Ultramicroscopy, Vol. 91 (1-4) (2002) pp. 253-259
    1438 Protein Stretching IV: Analysis of Force-Extension Curves
    A. Ikai and T. Wang
    Jpn. J. Appl. Phys., 39 (2000) 3784-3788
    1669 Antibody recognition imaging by force microscopy
    A. Raab, W. Han, D. Badt, S. J. Smith-Gill, S. M. Lindsay, H. Schindler and P. Hinterdorfer
    Nature Biotechnology, 17 (1999) 9, 902-905
    1710 Multi-bead-and-spring model to interpret protein detachment studied by AFM force spectroscopy
    Csilla Gergely, Joseph Hemmerle, Pierre Schaaf, J. K. Heinrich Horber, Jean-Claude Voegel, and Bernard Senger
    Biophys. J., 83 (2002) 706 - 722
    1716 Modeling AFM-induced PEVK extension and the reversible unfolding of Ig/FNIII domains in single and multiple titin molecules
    Bo Zhang and John Spencer Evans
    Biophys. J., 80 (2001) 597 - 605
    1717 Atomic force microscopy and electron microscopy analysis of retrovirus gag proteins assembled in vitro on lipid bilayers
    Guy Zuber and Eric Barklis
    Biophys. J., 78 (2000) 373 - 384
    1718 Structural studies of a crystalline insulin analog complex with protamine by atomic force microscopy
    Christopher M. Yip, Mark L. Brader, Bruce H. Frank, Michael R. DeFelippis, and Michael D. Ward
    Biophys. J., 78 (2000) 466 - 473
    1730 Measurement of membrane binding between recoverin, a calcium-myristoyl switch protein, and lipid bilayers by AFM-based force spectroscopy
    Philippe Desmeules, Michel Grandbois, Vladimir A. Bondarenko, Akio Yamazaki, and Christian Salesse
    Biophys. J., 82 (2002) 3343 - 3350
    1733 High-resolution imaging of antibodies by tapping-mode atomic force microscopy: attractive and repulsive tip-sample interaction regimes
    Alvaro San Paulo and Ricardo Garcia
    Biophys. J., 78 (2000) 1599 - 1605
    1741 Can non-mechanical proteins withstand force? Stretching barnase by atomic force microscopy and molecular dynamics simulation
    Robert B. Best, Bin Li, Annette Steward, Valerie Daggett, and Jane Clarke
    Biophys. J., 81 (2001) 2344 - 2356
    1742 Direct visualization of ligand-protein interactions using atomic force microscopy
    Calum S. Neish, Ian L. Martin, Robert M. Henderson, and J. Michael Edwardson
    Br. J. Pharmacol., 135 (2002) 1943 - 1950
    1744 Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kB transcriptional activation and cytokine secretion
    Chen-Hsiung Yeh, Lydia Sturgis, Joe Haidacher, Xue-Nong Zhang, Sidney J. Sherwood, Robert J. Bjercke, Ondrej Juhasz, Michael T. Crow, Ronald G. Tilton, and Larry Denner
    Diabetes, 50 (2001) 1495 - 1504
    1750 Sampling the conformational space of membrane protein surfaces with the AFM
    Simon Scheuring, Daniel J. Muller, Henning Stahlberg, Hans-Andreas Engel and Andreas Engel
    European Biophysics Journal, 31 (2002), 172-178
    1751 Two-dimensional crystals: a powerful approach to assess structure, function anddynamics of membrane proteins
    Henning Stahlberg, Dimitrios Fotiadis, Simon Scheuring, Herve Remigy, Thomas Braun, Kuora Mitsuoka, Yoshinori Fujiyoshi and Andreas Engel
    FEBS letters, 504 (2001) 3, 166-172
    1759 Multilayer formation upon compression of surfactant monolayers depends on protein concentration as well as lipid composition. An atomic force microscopy study
    Robert V. Diemel, Margot M. E. Snel, Alan J. Waring, Frans J. Walther, Lambert M. G. van Golde, Gunther Putz, Henk P. Haagsman, and Joseph J. Batenburg
    J. Biol. Chem, 277 (2002) 21179 - 21188
    1766 Atomic force microscopy with carbon nanotube probe resolves the subunit organization of protein complexes
    Ken I. Hohmura, Yutakatti Itokazu, Shige H. Yoshimura, Gaku Mizuguchi, Yu-suke Masamura, Kunio Takeyasu, Yasushi Shiomi, Toshiki Tsurimoto, Hidehiro Nishijima, Seiji Akita, and Yoshikazu Nakayama
    J. Electron Microsc. (Tokyo), 49 (2000) 415 - 421
    1783 Imaging streptavidin 2D-crystals on biotinylated lipid monolayers at high resolution with the atomic force microscope
    Simon Scheuring, Daniel J. Muller, Philippe Ringler, J. Bernard Heymann, and Andreas Engel
    Journal of Microscopy, 193 (1999) pp. 28-35
    1785 The aquaporin sidedness revisited
    Simon Scheuring, Peter Tittmann, Henning Stahlberg, Philippe Ringler, Mario Borgnia, Peter Agre, Heinz Gross, and Andreas Engel
    Journal of Molecular Biology, 299 (2000) 5, pp. 1271-1278
    1786 Direct observation of postadsorption aggregation of antifreeze glycoproteins on silicates
    Ph. Lavalle, A. L. DeVries, C.-C. C. Cheng, S. Scheuring, and J. J. Ramsden
    Langmuir, 16 (2000) 13, pp. 5785-5789
    1793 UV light-damaged DNA and its interaction with human replication protein A: an atomic force microscopy study
    M. Lysetska, A. Knoll, D. Boehringer, T. Hey, G. Krauss, and G. Krausch
    Nucleic Acids Res., 30 (2002) 2686 - 2691
    1800 Cadherin interaction probed by atomic force microscopy
    W. Baumgartner, P. Hinterdorfer, W. Ness, A. Raab, D. Vestweber, H. Schindler, and D. Drenckhahn
    PNAS, 97 (2000) 4005 - 4010
    1807 Stepwise unfolding of titin under force-clamp atomic force microscopy
    Andres F. Oberhauser, Paul K. Hansma, Mariano Carrion-Vazquez, and Julio M. Fernandez
    PNAS, 98 (2001) 468 - 472
    1810 Atomic force microscopy reveals the mechanical design of a modular protein
    Hongbin Li, Andres F. Oberhauser, Susan B. Fowler, Jane Clarke, and Julio M. Fernandez
    PNAS, 97 (2000) 6527 - 6531
    1812 Unbinding process of adsorbed proteins under external stress studied by atomic force microscopy spectroscopy
    C. Gergely, J.-C. Voegel, P. Schaaf, B. Senger, M. Maaloum, J. K. H. Horber, and J. Hemmerle
    PNAS, 97 (2000) 10802 - 10807
    1813 Unfolding mechanics of holo- and apocalmodulin studied by the atomic force microscope
    Rukman Hertadi and Atsushi Ikai
    Protein Sci., 11 (2002) 1532 - 1538
    1814 Versatile cloning system for construction of multimeric proteins for use in atomic force microscopy
    Annette Steward, Jose Luis Toca-Herrera, and Jane Clarke
    Protein Sci., 11 (2002) 2179 - 2183
    1816 Conformational changes, flexibilities and intramolecular forces observed on individual proteins using AFM
    Daniel J. Muller, Dimitrios Fotiadis, Clemens Moller, Simon Scheuring, and Andreas Engel
    Single Molecules 1 (2000) 2, 115-118
    1817 Single proteins observed by atomic force microscopy
    Simon Scheuring, Dimitrios Fotiadis, Clemens Moller, Shirley A. Muller, Andreas Engel and Daniel J. Muller
    Single Molecules 2 (2001) 2, 59-67
    1945 Atomic force microscopy of insulin single crystals: direct visualization of molecules and crystal growth
    C. M. Yip, M. D. Ward
    Biophys. J., 71 (1996) 2, 1071-1078
    2481 The discrimination of IgM and IgG type antibodies and Fab' and F(ab)2 antibody fragments on an industrial substrate using scanning force microscopy
    C. J. Roberts, M. C. Davies, S. J. Tendler, P. M. Williams, J. Davies, A. C. Dawkes, G. D. Yearwood, J. C. Edwards
    Ultramicroscopy, 62 (1996) 3, 149-155
    1958 Atomic force microscopy proposes a novel model for stem-loop structure that binds a heat shock protein in the Staphylococcus aureus HSP70 operon
    T. Ohta, S. Nettikadan, F. Tokumasu, H. Ideno, Y. Abe, M. Kuroda, H. Hayashi, K. Takeyasu
    Biochemical and Biophysical Research Communications, 226 (1996) 3, 730-734
    1973 Atomic force microscopy visualizes ATP-dependent dissociation of multimeric TATA-binding protein before translocation into the cell nucleus
    H. Oberleithner, S. Schneider, J. O. Bustamante
    Pflugers. Arch., 432 (1996) 5, 839-844
    1880 Aldosterone activates the nuclear pore transporter in cultured kidney cells imaged with atomic force microscopy
    G. Folprecht, S. Schneider, H. Oberleithner
    Pflugers. Arch., 432 (1996) 5, 831-838
    1946 Atomic Force Microscopy of Interfacial Protein Films
    A. P. Gunning, P. J. Wilde, D. C. Clark, V. J. Morris, M. L. Parker, P. A. Gunning
    J. Colloid. Interface. Sci., 183 (1996) 2, 600-602
    2171 Human low density lipoprotein and human serum albumin adsorption onto model surfaces studied by total internal reflection fluorescence and scanning force microscopy
    C. H. Ho, D. W. Britt, V. Hlady
    J. Mol. Recognit., 9 (1996) 5-6, 444-455
    2494 The nanometer-scale structure of amyloid-beta visualized by atomic force microscopy
    W. B. Stine, Jr., S. W. Snyder, U. S. Ladror, W. S. Wade, M. F. Miller, T. J. Perun, T. F. Holzman, G. A. Krafft
    J. Protein Chem., 15 (1996) 2, 193-203
    2090 Direct observation of protein secondary structure in gas vesicles by atomic force microscopy
    T. J. McMaster, M. J. Miles, A. E. Walsby
    Biophys. J., 70 (1996) 5, 2432-2436
    2006 Chaperonins GroEL and GroES: views from atomic force microscopy
    J. Mou, S. Sheng, R. Ho, Z. Shao
    Biophys. J., 71 (1996) 4, 2213-2221
    2115 Electron and atomic force microscopy of membrane proteins
    J. B. Heymann, D. J. Muller, K. Mitsuoka, A. Engel
    Current Opinion in Structural Biology, 7 (1997) 4, 543-549
    2188 Imaging of the Early Events of Classical Complement Activation Using Antibodies and Atomic Force Microscopy
    auml, B. livaara, A. Askendal, Lundstr, ouml, I. I. m, P. Tengvall
    J. Colloid. Interface. Sci., 187 (1997) 1, 121-127
    2508 Three dimensional structure of human fibrinogen under aqueous conditions visualized by atomic force microscopy
    R. E. Marchant, M. D. Barb, J. R. Shainoff, S. J. Eppell, D. L. Wilson, C. A. Siedlecki
    Thromb Haemost, 77 (1997) 6, 1048-1051
    2322 Observation of metastable Abeta amyloid protofibrils by atomic force microscopy
    J. D. Harper, S. S. Wong, C. M. Lieber, P. T. Lansbury
    Chem. Biol., 4 (1997) 2, 119-125
    2323 Observing interactions between the IgG antigen and anti-IgG antibody with AFM
    P. C. Zhang, C. Bai, P. K. Ho, Y. Dai, Y. S. Wu
    IEEE Eng Med Biol Mag, 16 (1997) 2, 42-46
    2150 Gi regulation of secretory vesicle swelling examined by atomic force microscopy
    B. P. Jena, S. W. Schneider, J. P. Geibel, P. Webster, H. Oberleithner, K. C. Sritharan
    Proc. Natl. Acad. Sci. USA, 94 (1997) 24, 13317-13322
    2379 Scanning (atomic) force microscopy imaging of earthworm haemoglobin calibrated with spherical colloidal gold particles
    S. Xu, M. F. Arnsdorf
    J. Microsc., 187 (1997) 1, 43-53
    2389 Scanning force microscopy of the interaction events between a single molecule of heavy meromyosin and actin
    H. Nakajima, Y. Kunioka, K. Nakano, K. Shimizu, M. Seto, T. Ando
    Biochemical and Biophysical Research Communications, 234 (1997) 1, 178-182
    2474 Tertiary structure of the hepatic cell protein fibrinogen in fluid revealed by atomic force microscopy
    D. J. Taatjes, A. S. Quinn, R. J. Jenny, P. Hale, E. G. Bovill, J. McDonagh
    Cell. Biol. Int., 21 (1997) 11, 715-726
    2093 Direct visualization of collagen-bound proteoglycans by tapping-mode atomic force microscopy
    M. Raspanti, A. Alessandrini, V. Ottani, A. Ruggeri
    J. Struct. Biol., 119 (1997) 2, 118-122
    1935 Atomic force microscopy of collagen molecules. Surface morphology of segment-long-spacing (SLS) crystallites of collagen
    Y. Fujita, K. Kobayashi, T. Hoshino
    J. Electron Microsc. (Tokyo), 46 (1997) 4, 321-6
    2371 Reversible unfolding of individual titin immunoglobulin domains by AFM
    M. Rief, M. Gautel, F. Oesterhelt, J. M. Fernandez, H. E. Gaub
    Science, 276 (1997) 5315, 1109-1112
    2218 Interaction of DNA-dependent protein kinase with DNA and with Ku: biochemical and atomic-force microscopy studies
    M. Yaneva, T. Kowalewski, M. R. Lieber
    EMBO J., 16 (1997) 16, 5098-5112
    2242 Ku proteins join DNA fragments as shown by atomic force microscopy
    D. Pang, S. Yoo, W. S. Dynan, M. Jung, A. Dritschilo
    Cancer. Res., 57 (1997) 8, 1412-1415
    2060 Cryo-atomic force microscopy of smooth muscle myosin
    Y. Zhang, Z. Shao, A. P. Somlyo, A. V. Somlyo
    Biophys. J., 72 (1997) 3, 1308-1318
    1869 AFM analysis of DNA-protamine complexes bound to mica
    M. J. Allen, E. M. Bradbury, R. Balhorn
    Nucleic Acids Res., 25 (1997) 11, 2221-2226
    2550 Visualization of poly(A)-binding protein complex formation with poly(A) RNA using atomic force microscopy
    B. L. Smith, D. R. Gallie, H. Le, P. K. Hansma
    J. Struct. Biol., 119 (1997) 2, 109-117
    2434 Structural and morphological characterization of ultralente insulin crystals by atomic force microscopy: evidence of hydrophobically driven assembly
    C. M. Yip, M. R. DeFelippis, B. H. Frank, M. L. Brader, M. D. Ward
    Biophys. J., 75 (1998) 3, 1172-1179
    1936 Atomic force microscopy of crystalline insulins: the influence of sequence variation on crystallization and interfacial structure
    C. M. Yip, M. L. Brader, M. R. DeFelippis, M. D. Ward
    Biophys. J., 74 (1998) 5, 2199-2209
    1915 Atomic force microscopy detects changes in the interaction forces between GroEL and substrate proteins
    A. Vinckier, P. Gervasoni, F. Zaugg, U. Ziegler, P. Lindner, P. Groscurth, A. Pluckthun, G. Semenza
    Biophys. J., 74 (1998) 6, 3256-3263
    2199 Imaging two-dimensional arrays of soluble proteins by atomic force microscopy in contact mode using a sharp supertip
    T. Furuno, H. Sasabe, A. Ikegami
    Ultramicroscopy, 70 (1998) 3, 125-131
    2490 The mechanical stability of immunoglobulin and fibronectin III domains in the muscle protein titin measured by atomic force microscopy
    M. Rief, M. Gautel, A. Schemmel, H. E. Gaub
    Biophys. J., 75 (1998) 6, 3008-3014
    2262 Mapping a protein-binding site on straightened DNA by atomic force microscopy
    H. Yokota, D. A. Nickerson, B. J. Trask, G. van den Engh, M. Hirst, I. Sadowski, R. Aebersold
    Anal. Biochem., 264 (1998) 2, 158-164
    2515 TM-AFM Threshold Analysis of Macromolecular Orientation: A Study of the Orientation of IgG and IgE on Mica Surfaces
    M. Bergkvist, J. Carlsson, T. Karlsson, S. Oscarsson
    J. Colloid. Interface. Sci., 206 (1998) 2, 475-481
    2319 Observation of geometric structure of collagen molecules by atomic force microscopy
    V. Baranauskas, B. C. Vidal, N. A. Parizotto
    Appl. Biochem. Biotechnol., 69 (1998) 2, 91-97
    2138 Fibrous long spacing collagen ultrastructure elucidated by atomic force microscopy
    M. F. Paige, J. K. Rainey, M. C. Goh
    Biophys. J., 74 (1998) 6, 3211-3216
    1981 Binding contribution between synaptic vesicle membrane and plasma membrane proteins in neurons: an AFM study
    K. C. Sritharan, A. S. Quinn, D. J. Taatjes, B. P. Jena
    Cell. Biol. Int., 22 (1998) 9-10, 649-655
    2155 Growth of Protein 2-D Crystals on Supported Planar Lipid Bilayers Imaged in Situ by AFM
    I. I. Reviakine, W. Bergsma-Schutter, A. Brisson
    J. Struct. Biol., 121 (1998) 3, 356-361
    2511 Thyroid stimulating hormone assays based on the detection of gold conjugates by scanning force microscopy
    A. Perrin, A. Theretz, B. Mandrand
    Anal. Biochem., 256 (1998) 2, 200-206
    2412 Simultaneous height and adhesion imaging of antibody-antigen interactions by atomic force microscopy
    O. H. Willemsen, M. M. Snel, K. O. van der Werf, B. G. de Grooth, J. Greve, P. Hinterdorfer, H. J. Gruber, H. Schindler, Y. van Kooyk, C. G. Figdor
    Biophys. J., 75 (1998) 5, 2220-2228
    2553 Visualization of trp repressor and its complexes with DNA by atomic force microscopy
    E. Margeat, C. Le Grimellec, C. A. Royer
    Biophys. J., 75 (1998) 6, 2712-2720
    2174 Identification of microphases in mixed alpha- and omega-gliadin protein films investigated by atomic force microscopy
    T. J. McMaster, M. J. Miles, L. Wannerberger, A. C. Eliasson, P. R. Shewry, A. S. Tatham
    J. Agric. Food. Chem., 47 (1999) 12, 5093-5099
    2182 Imaging of collagen type III in fluid by atomic force microscopy
    D. J. Taatjes, A. S. Quinn, E. G. Bovill
    Microsc. Res. Tech., 44 (1999) 5, 347-352
    2302 Monitoring the assembly of Ig light-chain amyloid fibrils by atomic force microscopy
    C. Ionescu-Zanetti, R. Khurana, J. R. Gillespie, J. S. Petrick, L. C. Trabachino, L. J. Minert, S. A. Carter, A. L. Fink
    Proc. Natl. Acad. Sci. USA, 96 (1999) 23, 13175-13179
    2234 Investigation of protein partnerships using atomic force microscopy
    D. J. Ellis, T. Berge, J. M. Edwardson, R. M. Henderson
    Microsc. Res. Tech., 44 (1999) 5, 368-377
    2369 Reflection interference contrast microscopy combined with scanning force microscopy verifies the nature of protein-ligand interaction force measurements
    J. K. Stuart, V. Hlady
    Biophys. J., 76 (1999) 1/1, 500-508
    2077 Determining the molecular-packing arrangements on protein crystal faces by atomic force microscopy
    H. Li, M. A. Perozzo, J. H. Konnert, A. Nadarajah, M. L. Pusey
    Acta Crystallogr. D: Biol. Crystallogr., 55 (1999) 5, 1023-1035
    1953 Atomic force microscopy of the submolecular architecture of hydrated ocular mucins
    T. J. McMaster, M. Berry, A. P. Corfield, M. J. Miles
    Biophys. J., 77 (1999) 1, 533-541
    1914 Atomic force microscopy captures length phenotypes in single proteins
    M. Carrion-Vazquez, P. E. Marszalek, A. F. Oberhauser, J. M. Fernandez
    Proc. Natl. Acad. Sci. USA, 96 (1999) 20, 11288-11292
    1876 AFM study of membrane proteins, cytochrome P450 2B4, and NADPH-cytochrome P450 reductase and their complex formation
    O. I. Kiselyova, I. V. Yaminsky, Y. D. Ivanov, I. P. Kanaeva, V. Y. Kuznetsov, A. I. Archakov
    Arch. Biochem. Biophys., 371 (1999) 1, 1-7
    1982 Binding forces of hepatic microsomal and plasma membrane proteins in normal and pancreatitic rats: an AFM force spectroscopic study
    L. A. Slezak, A. S. Quinn, K. C. Sritharan, J. P. Wang, G. Aspelund, D. J. Taatjes, D. K. Andersen
    Microsc. Res. Tech., 44 (1999) 5, 363-367
    2560 Watching amyloid fibrils grow by time-lapse atomic force microscopy
    C. Goldsbury, J. Kistler, U. Aebi, T. Arvinte, G. J. Cooper
    J. Mol. Biol., 285 (1999) 1, 33-39
    2103 Dynamics of astrocyte adhesion as analyzed by a combination of atomic force microscopy and immuno-cytochemistry: the involvement of actin filaments and connexin 43 in the early stage of adhesion
    Y. Yamane, H. Shiga, H. Asou, H. Haga, K. Kawabata, K. Abe, E. Ito
    Arch. Histol. Cytol., 62 (1999) 4, 355-361
    2076 Determining the molecular-growth mechanisms of protein crystal faces by atomic force microscopy
    H. Li, A. Nadarajah, M. L. Pusey
    Acta Crystallogr. D: Biol. Crystallogr., 55 (1999) 5, 1036-1045
    2414 Single integrin molecule adhesion forces in intact cells measured by atomic force microscopy
    P. P. Lehenkari, M. A. Horton
    Biochemical and Biophysical Research Communications, 259 (1999) 3, 645-650
    2088 Direct measurement of the viscoelasticity of adsorbed protein layers using atomic force microscopy
    C. Nemes, N. Rozlosnik, J. J. Ramsden
    Phys. Rev. E: Stat. Phys. Plasmas Fluids Relat. Interdiscip. Topics, 60 (1999) 2/A, R1166-R1169
    2468 Surface-dependent conformations of human fibrinogen observed by atomic force microscopy under aqueous conditions
    P. S. Sit, R. E. Marchant
    Thromb Haemost, 82 (1999) 3, 1053-1060
    2095 Disulfide bonds in the outer layer of keratin fibers confer higher mechanical rigidity: correlative nano-indentation and elasticity measurement with an AFM
    A. N. Parbhu, W. G. Bryson, R. Lal
    Biochemistry, 38 (1999) 36, 11755-11761
    2429 Spin-stretching of DNA and protein molecules for detection by fluorescence and atomic force microscopy
    H. Yokota, J. Sunwoo, M. Sarikaya, G. van den Engh, R. Aebersold
    Anal. Chem., 71 (1999) 19, 4418-4422
    2092 Direct observation of the anchoring process during the adsorption of fibrinogen on a solid surface by force-spectroscopy mode atomic force microscopy
    J. Hemmerle, S. M. Altmann, M. Maaloum, J. K. Horber, L. Heinrich, J. C. Voegel, P. Schaaf
    Proc. Natl. Acad. Sci. USA, 96 (1999) 12, 6705-6710
    2032 Collagen II containing a Cys substitution for Arg-alpha1-519. Analysis by atomic force microscopy demonstrates that mutated monomers alter the topography of the surface of collagen II fibrils
    E. Adachi, O. Katsumata, S. Yamashina, D. J. Prockop, A. Fertala
    Matrix. Biol., 18 (1999) 2, 189-196
    2473 Tapping-mode atomic force microscopy produces faithful high-resolution images of protein surfaces
    C. Moller, M. Allen, V. Elings, A. Engel, D. J. Muller
    Biophys. J., 77 (1999) 2, 1150-1158
    2419 Single protein misfolding events captured by atomic force microscopy
    A. F. Oberhauser, P. E. Marszalek, M. Carrion-Vazquez, J. M. Fernandez
    Nat. Struct. Biol., 6 (1999) 11, 1025-1028
    2465 Surface topography of the p3 and p6 annexin V crystal forms determined by atomic force microscopy
    I. Reviakine, W. Bergsma-Schutter, C. Mazeres-Dubut, N. Govorukhina, A. Brisson
    J. Struct. Biol., 131 (2000) 3, 234-239
    2081 Different patterns of collagen-proteoglycan interaction: a scanning electron microscopy and atomic force microscopy study
    M. Raspanti, T. Congiu, A. Alessandrini, P. Gobbi, A. Ruggeri
    Eur. J. Histochem., 44 (2000) 4, 335-343
    2176 Imaging and mapping heparin-binding sites on single fibronectin molecules with atomic force microscopy
    H. Lin, R. Lal, D. O. Clegg
    Biochemistry, 39 (2000) 12, 3192-3196
    1954 Atomic force microscopy of the three-dimensional crystal of membrane protein, OmpC porin
    H. Kim, R. M. Garavito, R. Lal
    Colloids. Surf. B. Biointerfaces, 19 (2000) 4, 347-355
    2080 Differences in zero-force and force-driven kinetics of ligand dissociation from beta-galactoside-specific proteins (plant and animal lectins, immunoglobulin G) monitored by plasmon resonance and dynamic single molecule force microscopy
    W. Dettmann, M. Grandbois, S. Andre, M. Benoit, A. K. Wehle, H. Kaltner, H. J. Gabius, H. E. Gaub
    Arch. Biochem. Biophys., 383 (2000) 2, 157-170
    2123 Energy landscape of streptavidin-biotin complexes measured by atomic force microscopy
    C. Yuan, A. Chen, P. Kolb, V. T. Moy
    Biochemistry, 39 (2000) 33, 10219-10223
    2210 Individual plasma proteins detected on rough biomaterials by phase imaging AFM
    N. B. Holland, R. E. Marchant
    J. Biomed. Mater. Res., 51 (2000) 3, 307-315
    2059 Cryoatomic force microscopy of filamentous actin
    Z. Shao, D. Shi, A. V. Somlyo
    Biophys. J., 78 (2000) 2, 950-958
    1977 Atomic force microscopy-based detection of binding and cleavage site of matrix metalloproteinase on individual type II collagen helices
    H. B. Sun, G. N. Smith, Jr., K. A. Hasty, H. Yokota
    Anal. Biochem., 283 (2000) 2, 153-158
    2215 In-situ atomic force microscopy study of beta-amyloid fibrillization
    H. K. Blackley, G. H. Sanders, M. C. Davies, C. J. Roberts, S. J. Tendler, M. J. Wilkinson
    J. Mol. Biol., 298 (2000) 5, 833-840
    1941 Atomic force microscopy of gastric mucin and chitosan mucoadhesive systems
    M. P. Deacon, S. McGurk, C. J. Roberts, P. M. Williams, S. J. Tendler, M. C. Davies, S. S. Davis, S. E. Harding
    Biochem. J., 348 (2000) 3, 557-63
    2502 The subfibrillar arrangement of corneal and scleral collagen fibrils as revealed by scanning electron and atomic force microscopy
    S. Yamamoto, H. Hashizume, J. Hitomi, M. Shigeno, S. Sawaguchi, H. Abe, T. Ushiki
    Arch. Histol. Cytol., 63 (2000) 2, 127-135
    2532 Unfolding forces of titin and fibronectin domains directly measured by AFM
    M. Rief, M. Gautel, H. E. Gaub
    Adv. Exp. Med. Biol., 481 (2000) 129-36 (discussion 137-141)
    2391 Scanning force microscopy reveals structural alterations in diabetic rat collagen fibrils: role of protein glycation
    P. Odetti, I. Aragno, R. Rolandi, S. Garibaldi, S. Valentini, L. Cosso, N. Traverso, D. Cottalasso, M. A. Pronzato, U. M. Marinari
    Diabetes. Metab. Res. Rev., 16 (2000) 2, 74-81
    1865 Adsorbed Layers of Ferritin at Solid and Fluid Interfaces Studied by Atomic Force Microscopy
    C. A. Johnson, Y. Yuan, A. M. Lenhoff
    J. Colloid. Interface. Sci., 223 (2000) 2, 261-272
    2266 Mapping interfacial chemistry induced variations in protein adsorption with scanning force microscopy
    T. C. Ta, M. T. McDermott
    Anal. Chem., 72 (2000) 11, 2627-2634
    2353 Probing protein-peptide-protein molecular architecture by atomic force microscopy and surface plasmon resonance
    M. M. Stevens, S. Allen, W. C. Chan, M. C. Davies, C. J. Roberts, S. J. Tendler, P. M. Williams
    Analyst, 125 (2000) 2, 245-250
    2405 Self-assembly properties of recombinant engineered amelogenin proteins analyzed by dynamic light scattering and atomic force microscopy
    J. Moradian-Oldak, M. L. Paine, Y. P. Lei, A. G. Fincham, M. L. Snead
    J. Struct. Biol., 131 (2000) 1, 27-37
    2321 Observation of human corneal and scleral collagen fibrils by atomic force microscopy
    S. Yamamoto, J. Hitomi, S. Sawaguchi, H. Abe, M. Shigeno, T. Ushiki
    Jpn. J. Ophthalmol., 44 (2000) 3, 318
    1846 X-ray diffraction and atomic force microscopy analysis of twinned crystals: rhombohedral canavalin
    T. P. Ko, Y. G. Kuznetsov, A. J. Malkin, J. Day, A. McPherson
    Acta Crystallogr. D: Biol. Crystallogr., 57 (2001) 6, 829-839
    2530 Ultrastructure and assembly of segmental long spacing collagen studied by atomic force microscopy
    M. F. Paige, M. C. Goh
    Micron, 32 (2001) 3, 355-361
    2427 Spin-column isolation of DNA-protein interactions from complex protein mixtures for AFM imaging
    P. R. Hoyt, M. J. Doktycz, R. J. Warmack, D. P. Allison
    Ultramicroscopy, 86 (2001) 1-2, 139-143
    1858 A tapping mode AFM study of collapse and denaturation in dentinal collagen
    F. El Feninat, T. H. Ellis, E. Sacher, I. Stangel
    Dent. Mater., 17 (2001) 4, 284-288
    2554 Visualizing filamentous actin on lipid bilayers by atomic force microscopy in solution
    D. Shi, A. V. Somlyo, A. P. Somlyo, Z. Shao
    J. Microsc., 201 (2001) 3, 377-382
    2466 Surface ultrastructure of collagen fibrils and their association with proteoglycans in human cornea and sclera by atomic force microscopy and energy-filtering transmission electron microscopy
    A. Miyagawa, M. Kobayashi, Y. Fujita, O. Hamdy, K. Hirano, M. Nakamura, Y. Miyake
    Cornea, 20 (2001) 6, 651-656
    2421 Single-molecule imaging by atomic force microscopy of the native chaperonin complex of the thermophilic archaeon Sulfolobus solfataricus
    F. Valle, G. Dietler, P. Londei
    Biochemical and Biophysical Research Communications, 288 (2001) 1, 258-262
    1948 Atomic force microscopy of nonhydroxy galactocerebroside nanotubes and their self-assembly at the air-water interface, with applications to myelin
    B. Ohler, I. Revenko, C. Husted
    J. Struct. Biol., 133 (2001) 1, 1-9
    2349 Potential-induced resonant tunneling through a redox metalloprotein investigated by electrochemical scanning probe microscopy
    P. Facci, D. Alliata, S. Cannistraro
    Ultramicroscopy, 89 (2001) 4, 291-298
    2177 Imaging and mapping protein-binding sites on DNA regulatory regions with atomic force microscopy
    F. Moreno-Herrero, P. Herrero, J. Colchero, A. M. Baro, F. Moreno
    Biochemical and Biophysical Research Communications, 280 (2001) 1, 151-157
    1846 X-ray diffraction and atomic force microscopy analysis of twinned crystals: rhombohedral canavalin
    T. P. Ko, Y. G. Kuznetsov, A. J. Malkin, J. Day, A. McPherson
    Acta Crystallogr. D: Biol. Crystallogr., 57 (2001) 6, 829-839
    2195 Imaging the native structure of the chaperone protein GroEL without fixation using atomic force microscopy
    F. Valle, J. A. Derose, G. Dietler, M. Kawe, A. Pluckthun, G. Semenza
    J. Microsc., 203 (2001) 2, 195-198
    1866 Adsorption and Bioactivity of Protein A on Silicon Surfaces Studied by AFM and XPS
    M. C. Coen, R. Lehmann, P. Groning, M. Bielmann, C. Galli, L. Schlapbach
    J. Colloid. Interface. Sci., 233 (2001) 2, 180-189
    1872 AFM imaging in solution of protein-DNA complexes formed on DNA anchored to a gold surface
    O. Medalia, J. Englander, R. Guckenberger, J. Sperling
    Ultramicroscopy, 90 (2001) 2-3, 103-112
    1856 A study of fibrous long spacing collagen ultrastructure and assembly by atomic force microscopy
    M. F. Paige, J. K. Rainey, M. C. Goh
    Micron, 32 (2001) 3, 341-353
    2356 Progressive accretion of amelogenin molecules during nanospheres assembly revealed by atomic force microscopy
    H. B. Wen, A. G. Fincham, J. Moradian-Oldak
    Matrix. Biol., 20 (2001) 5-6, 387-395
    1892 Analysis of protein crystal growth at molecular resolution by atomic force microscopy
    M. Wiechmann, O. Enders, C. Zeilinger, H. A. Kolb
    Ultramicroscopy, 86 (2001) 1-2, 159-166
    2232 Investigation of microcontact transfer of proteins from a selectively plasma treated elastomer stamp by fluorescence microscopy and force microscopy
    X. Feng, C. J. Roberts, D. A. Armitage, M. C. Davies, S. J. Tendler, S. Allen, P. M. Williams
    Analyst, 126 (2001) 7, 1100-1104
    1909 Atomic force microscopy and proteins
    L. P. da Silva
    Protein Pept. Lett., 9 (2002) 2, 117-126
    2049 Conformations, flexibility, and interactions observed on individual membrane proteins by atomic force microscopy
    D. J. Muller, A. Engel
    Methods Cell Biol., 68 (2002) 257-299
    1845 What can atomic force microscopy tell us about protein folding?
    R. B. Best, J. Clarke
    Chem. Commun. (Cambridge), 3 (2002) , 183-192
    1983 Binding of dentin noncollagenous matrix proteins to biological mineral crystals: an atomic force microscopy study
    M. L. Wallwork, J. Kirkham, H. Chen, S. X. Chang, C. Robinson, D. A. Smith, B. H. Clarkson
    Calcif. Tissue. Int., 71 (2002) 3, 249-255
    2561 What can atomic force microscopy tell us about protein folding?
    R. B. Best, J. Clarke
    Chem. Commun. (Cambridge), 3 (2002) 183-192
    2498 The scanning probe microscopy of metalloproteins and metalloenzymes
    J. J. Davis, H. A. Hill
    Chem. Commun. (Cambridge), 5 (2002) 393-401
    2435 Structural aspects of the extracellular matrix of the tendon: an atomic force and scanning electron microscopy study
    M. Raspanti, T. Congiu, S. Guizzardi
    Arch. Histol. Cytol., 65 (2002) 1, 37-43
    2320 Observation of human corneal and scleral collagen fibrils by atomic force microscopy
    S. Yamamoto, J. Hitomi, S. Sawaguchi, H. Abe, M. Shigeno, T. Ushiki
    Jpn. J. Ophthalmol., 46 (2002) 5, 496-501
    2320 The backbone conformational entropy of protein folding: experimental measures from atomic force microscopy
    J. B. Thompson, H. G. Hansma, P. K. Hansma, K. W. Plaxco
    J. Mol. Biol., 322 (2002) 3, 645-652
    2417 Single molecule recognition of protein binding epitopes in brush border membranes by force microscopy
    S. Wielert-Badt, P. Hinterdorfer, H. J. Gruber, J. T. Lin, D. Badt, B. Wimmer, H. Schindler, R. K. Kinne
    Biophys. J., 82 (2002) 5, 2767-2774
    1984 Binding of discoidin domain receptor 2 to collagen I: an atomic force microscopy investigation
    G. Agarwal, L. Kovac, C. Radziejewski, S. J. Samuelsson
    Biochemistry, 41 (2002) 37, 11091-11098
    2416 Single molecule imaging of supported planar lipid bilayer--reconstituted human insulin receptors by in situ scanning probe microscopy
    A. Slade, J. Luh, S. Ho, C. M. Yip
    J. Struct. Biol., 137 (2002) 3, 283-291
    2140 Fine-stranded and particulate aggregates of heat-denatured whey proteins visualized by atomic force microscopy
    S. Ikeda, V. J. Morris
    Biomacromolecules, 3 (2002) 2, 382-389
    2324 Observing structure, function and assembly of single proteins by AFM
    D. J. Muller, H. Janovjak, T. Lehto, L. Kuerschner, K. Anderson
    Prog. Biophys. Mol. Biol., 79 (2002) 1-3, 1-43
    2192 Imaging real-time aggregation of amyloid beta protein (1-42) by atomic force microscopy
    A. Parbhu, H. Lin, J. Thimm, R. Lal
    Peptides, 23 (2002) 7, 1265-1270
    2276 Mechanical unfolding of a titin Ig domain: structure of unfolding intermediate revealed by combining AFM, molecular dynamics simulations, NMR and protein engineering
    S. B. Fowler, R. B. Best, J. L. Toca Herrera, T. J. Rutherford, A. Steward, E. Paci, M. Karplus, J. Clarke
    J. Mol. Biol., 322 (2002) 4, 841-849
    2194 Imaging the electrostatic potential of transmembrane channels: atomic probe microscopy of OmpF porin
    A. Philippsen, W. Im, A. Engel, T. Schirmer, B. Roux, D. J. Muller
    Biophys. J., 82 (2002) 3, 1667-1676
    2227 Investigating the ultrastructure of fibrous long spacing collagen by parallel atomic force and transmission electron microscopy
    A. C. Lin, M. C. Goh
    Proteins, 49 (2002) 3, 378-384
    2202 In situ atomic force microscopy of partially demineralized human dentin collagen fibrils
    S. Habelitz, M. Balooch, S. J. Marshall, G. Balooch, G. W. Marshall, Jr.
    J. Struct. Biol., 138 (2002) 3, 227-236
    2489 The mechanical hierarchies of fibronectin observed with single-molecule AFM
    A. F. Oberhauser, C. Badilla-Fernandez, M. Carrion-Vazquez, J. M. Fernandez
    J. Mol. Biol., 319 (2002) 2, 433-447
    2563 Improvements in atomic force microscopy protocols for imaging fibrous proteins
    P. Hallett, L. Tskhovrebova, J. Trinick, G. Offer, M. J. Miles
    J. Vac. Sci. Technol., B14 (1996) 2, 1444-1448
    2642 The study of protein mechanics with the atomic force microscope
    Fisher T.E., Oberhauser A.F., Carrion-Vazquez M., Marszalek P.E., Fernandez J.M.
    Trends Biochem. Sci., 24 (1999) 379-384