Local electrostatic properties play a central role in a variety of biological processes. A detailed characterization of the structure and function of biological systems requires an understanding of the strength and location of their electro-static interactions. Many techniques exist for measuring the electrostatic properties of biological molecules, such as electrophoretic, titration, electrokinetic, and redox potential measurements;however,relativelyfewexperimentalmethods can determine the spatial distribution of charge on surfaces, such as membrane proteins (McLaughlin, 1989; Cevc, 1990).
Cationic ferritin can label negative charges on membranes and cell surfaces and be visualized with electron microscopy (Danon et al., 1972). In solution, local ionic currents are measured with the vibrating probe (Jaffe and Nuccitelli, 1974)andthescanningion-conductancemicroscope(Hansma et al., 1989). The AFM tip is sensitive to electrostatic inter-actions with a sample surface in solution; it can therefore provide quantitative information about surface charge den-sities of proteins with high spatial resolution.
Quantitative electrostatic measurements with the AFM are based on forces produced from overlapping electrical double layers as a charged probe is brought near a charged sample surface (Fig. 16). This paradigm was initially developed for other experimental approaches, and has been particularly well utilized with the surface forces apparatus (SFA).The SFA work has shown that the Derjaguin, Landau, Verwey, and Overbeek Theory (DLVO theory) can be used to relate force measurements to surface charge (Israelachvili and Adams, 1977; Israelachvili, 1992). It has since been shown that DLVO theory can be applied to AFM measure-ments (Ducker et al., 1991). Subsequently, a number of groups have measured surface charge density and Debye length as a function of pH, electrolyte type, and concentra-tion with the AFM and found agreement with standard DLVO theory for measurements over sample surfaces (Ducker et al., 1991; Hillier et al., 1996; Larson et al., 1997;
Biggs and Pround, 1997). All these measurements are based on fitting force-distance curves to DLVO theory and thus require a measurement of the tip-sample separation distance.
4.3.2. Theory
Electrostatic interactions measured using AFM are most commonly covered by the continuum DLVO theory (Israelachvili, 1992). Here, the interplay between the electro-static double layer (EDL) force (Fele) and the van der Waals force (Fvdw) is described, neglecting effects of ion radii, hydration forces, steric forces and specific interactions (Israelachvili and Adams, 1977; Pashley, 1981; Butt, 1991b;
Israelachvili, 1992). The interaction force that arises from overlapping double layers when one charged surface (an
AFM tip) is brought close enough to a second surface (e.g., protein molecules), is directly related to the charge density on or the potential of the two surfaces. While the two limits of the theory, constant charge and constant potential, diverge for small separations, they quickly converge at separations greater than several nanometers (Israelachvili, 1992). If we consider the AFM tip as a sphere and the sample as a flat plane, then the total force, F, is described by
F(d) = Fele (d) +Fvdw(d) = 4πRλσpσt
εeε0 ⋅e−d /λ−HaR
6 d2 [5]
where R is the radius of the sphere, d the tip-sample separation distance, σt the surface charge density of the sphere, σp the surface charge density of the biomolecular plane, εe the dielectric constant of the medium, εo the permittivity of the free space, λ Debye length, and Ha is the Hamaker constant . Equation [5] holds so long as R, λ, σt, and σp do not vary significantly with d. We note that explicitly modeling the tip as an inverted pyramid instead of a sphere adds to Eq. [5] a geometrical factor independent of d that does not affect subsequent calculations (Butt, 1991b, 1992). The Debye length λ characterizes the exponential decrease of the potential resulting from screening the surface charges with electrolytes, with λ = 0.304 nm/√C for mono-valent and 0.174 nm/√C for dimono-valent (1:2 or 2:1) electrolytes.
Hence, if the electrolyte composition and pH of the buffer solution are known, the measured exponential decay of the force can be fitted to reveal the surface charge density of the object (Israelachvili, 1992).
4.3.3. Measurement
The AFM can be used to map the spatial distribution of surface charge by (1) using isoforce images based on a
repulsive double-layer force or (2) using arrays of force-distance curves. Force force-distance curves are used to examine the spatial distribution of surface charge density and large arrays of force curves are used to map charge distribution of biological materials. All these measurements of electrostatic force are based on fitting force-distance curves to DLVO theory and thus require an absolute measurement of the tip-sample separation distance, D. Because current AFM have no method independent of the tip-sample interaction to determine D, in practice force-distance curves have to include tip-sample contact. In this mode of electrostatic force mapping, force curves are usually taken while the AFM tip is scanned by a piezoelectric scanner across the sample.
4.3.4. Examples
The AFM probes have been used as sensors to probe charges of biological surfaces immersed in buffer solution (Butt et al., 1995). The electrostatic double-layer force (Israelachvili, 1992) interacting between the charged probe and charged regions of the biological sample can contribute significantly to the AFM topograph recorded (Muller and Engel, 1997; Rotsch and Radmacher, 1997) and can be tuned by the electrolyte concentration and the pH of the buffer solution. The DLVO theory describes the exponential decay of the electrostatic double-layer force as a function of the surface separation (Israelachvili, 1992). Whereas AFM probes have been used to measure the average surface char-ges from force-distance curves (Butt, 1991a, b; Ducker et al., 1991), surface charge maps have been obtained at 40-nm lateral resolution by recording force-distance curves at each pixel of the sampled surface (Rotsch and Radmacher, 1997;
Heinz and Hoh, 1999b).
Fig. (16). Force mapping interactions between AFM tip and protein sample in buffer solution. (A) The electrostatic double-layer force interacts via long-range forces with a relatively large area of the protein assembly. The force effectively interacting at the AFM tip apex is a composite of all interacting forces. (B) Scanning a negatively charged AFM silicon nitride tip over an electrically neutral surface reveals the true topography. (C) In case of negative charge of protein as the sample, the AFM tip detects local electrostatic repulsions. The resulting topograph represents a mixture of height and electrostatic information.
Electrostatic Potential Mapping of Channel-Forming Protein OmpF Porin
Philippsen and coworkers (2002) used AFM to image native transmembrane channel-forming protein OmpF porin located in the outer membrane of E. coli and to determine the electrostatic potential generated by the protein (Fig. 17). The OmpF porin trimers were imaged at a lateral resolution of
~0.5 nm and a vertical resolution of ~0.1 nm at variable electrolyte concentrations of the buffer solution. Differences measured between topographs recorded at variable ionic strength allowed the electrostatic potential mapping of OmpF porin. The potential map acquired by AFM showed quali-tative agreement with continuum electrostatic calculations based on the atomic OmpF porin embedded in a lipid bilayer at the same electrolyte concentrations. This method opens a novel avenue to determine the electrostatic potential of native protein surfaces at a lateral resolution better than 1 nm and a vertical resolution of ~0.1 nm.
CONCLUSION
AFM has opened an innovative approach to investigating directly the ranges and magnitudes of the interaction forces between protein and other molecules. It has also proved its value not only for resolving the topographical structure of protein samples, but also for imaging and mapping the forces that control mechanical properties of proteins under physiol-ogical conditions. In addition, it allows individual protein molecules and complexes to be stretched and disrupted for measuring the forces, which stabilize protein structure directly on a single molecule. A major advantage of AFM over other techniques is its lateral resolution which is of paramount importance at the µm and nm scale. However, AFM has the disadvantage that it is a surface technique for force measurement, implying that force is generated in only one direction. Especially in the case of rupture force measurements, this might not be the energetically mostly preferred way to separate complexes. Compared to other nanoscopic force measurement devices, such as optical and magnetic trapping and micropipettes, another disadvantage of AFM is that the hydrodynamic damping is higher than in bulk liquid, and thus the force sensitivity is intrinsically lower than those other techniques. Nevertheless, AFM might be the most suitable technique to study a variety of different biological problems, whether they are structural, molecular interactions or dynamical measurements. AFM will prove to be a valuable technique for proteomics with its own unique contributions to our comprehension of the principles of protein folding and recognition.
ACKNOWLEDGEMENT
This work was supported by MEA (Grand 92-EC-17-A-05-S1-0017) and NSC (Grand 2320-B-002-003 and 93-2323-B-002-013). The authors thank Dr Liang-Ping Lin and Dr Su-Ming Hsu.
ABBREVIATIONS
AFM = Atomic force microscopy BSA = Bovine serum albumin
DLVO = Derjaguin, Landau, Verwey, and Overbeek
DSP = Digital signal processor HV = High voltage
ICAM1 = Intercellular adhesion molecule-1 PBS = Phosphate buffered saline pN = Piconewton
SFA = Surface forces apparatus STM = Scanning tunneling microscopy REFERENCES
Allen, S., Davies, J., Dawkes, A.C., Davies, M.C., Edwards, J.C., Parker, M.C., Roberts, C.J., Sefton, J., et al. (1996). In situ observation of streptavidin-biotin binding on an immunoassay well surface using an atomic force microscope. FEBS Lett. 390: 161-4.
Allen, S., Chen, X., Davies, J., Davies, M.C., Dawkes, A.C., Edwards, J.C., Roberts, C.J., Sefton, J., et al. (1997). Detection of antigen-antibody binding events with the atomic force microscope. Biochemistry 36:
7457-3.
Aranda-Espinoza, H., Carl, P., Leterrier, J.F., Janmey, P. and Discher, D.E.
(2002). Domain unfolding in neurofilament sidearms: effects of phosphorylation and ATP. FEBS Lett. 531: 397-401.
Baselt, D.R. (1994). Imaging spectroscopy with the atomic force microscope. J. Appl. Phys. 76: 33-8.
Baumgartner, W., Hinterdorfer, P., Ness, W., Raab, A., Vestweber, D., Schindler, H. and Drenckhahn, D. (2000). Cadherin interaction probed by atomic force microscopy. Proc. Natl. Acad. Sci. USA 97: 4005-10.
Bell, G.I. (1978). Models for the specific adhesion of cells to cells. Science 200: 618-27.
Berry, M., McMaster, T.J., Corfield, A.P. and Miles, M.J. (2001). Exploring the molecular adhesion of ocular mucins. Biomacromolecules 2: 498-503.
Biggs, S. and Proud, A.D. (1997). Forces between silica surfaces in aqueous solutions of a weak polyelectrolyte. Langmuir 13: 7202-10.
Binnig, G., Rohrer, H., Gerber, Ch. and E. Weibel, E. (1982). Tunneling through a controllable vacuum gap. Appl. Phys. Lett. 40: 178-80.
Binnig, G., Quate, C.F. and Gerber, Ch. (1986). Atomic force microscope.
Phys. Rev. Lett. 56: 930-3.
Braunewell, K.H. and Gundelfinger, E.D.(1999). Intracellular neuronal calcium sensor proteins: a family of EF-hand calcium-binding proteins in search of a function. Cell Tissue Res. 295: 1-12.
Burnham, N.A. and Colton, R.J. (1993). In Scanning Tunneling Microscopy and Spectroscopy. (Bonnell, D.A., Ed., VCH Publisher). New York, pp 191.
Butt, H.J. (1991a). Measuring electrostatic, van der Waals, and hydration forces in electrolyte solution with an atomic force microscope. Biophys.
J. 60: 1438-44.
Butt, H.J. (1991b). Electrostatic interactions in atomic force microscopy.
Biophys. J. 60: 777-85.
Butt, H.J. (1992). Measuring local surface charge densities in electrolyte solutions with a scanning force microscope. Biophys. J. 63: 578-82.
Butt, H.J., Jaschke, M. and Ducker, W. (1995). Measuring surface forces in aqueous solution with the atomic force microscope. Bioelect. Bioenerg.
38: 191-201.
Cai, X.E and Yang, J. (2003). The binding potential between the cholera toxin B-oligomer and its receptor. Biochemistry 42: 4028-34.
Carrion-Vazquez, M., Marszalek, P.E., Oberhauser, A.F. and Fernandez, J.M. (1999). Atomic force microscopy captures length phenotypes in single proteins. Proc. Natl. Acad. Sci. USA 96: 11288-92.
Carrion-Vazquez, M., Oberhauser, A.F., Fisher, T.E., Marszalek, P.E., Li, H. and Fernandez, J.M. (2000). Mechanical design of proteins studied by single-molecule force spectroscopy and protein engineering. Prog.
Biophys. Mol. Biol. 74: 63-91.
Cevc, G. (1990). Membrane electrostatics. Biochim. Biophys. Acta 1031:
311–82.
Chen, A. and Moy, V.T. (2000). Cross-linking of cell surface receptors enhances cooperativity of molecular adhesion. Biophys. J. 78: 2814-20.
Chen, C.H., Vesecky, S.M. and Gewirth, A.A. (1992). In situ atomic force microscopy of underpotential deposition of silver on gold(111). J. Am.
Chem. Soc. 114: 451-8.
Chilkoti, A., Boland, T., Ratner, B.D. and Stayton, P.S. (1995). The relationship between ligand-binding thermodynamics and
protein-ligand interaction forces measured by atomic force microscopy.
Biophys. J. 69: 2125-30.
Chothia, C. and Jones, E.Y. (1997). The molecular structure of cell adhesion molecules. Annu. Rev. Biochem. 66: 823-62.
Cleveland, J.P., Manne, S., Bocek, D. and Hansma, P.K. (1993) A nondestructive method for determining the spring constant of cantilevers for scanning force microscopy. Rev. Sci. Instru. 64: 403-5.
Creuzet, F., Ryschenkow, G. and Arribart, H. (1992). J. Adhes. 40: 15-22.
Dammer, U., Popescu, O., Wagner, P., Anselmetti, D., Guntherodt, H.J. and Misevic, G.N. (1995a) Binding strength between cell adhesion proteoglycans measured by atomic force microscopy. Science 267:
1173-5.
Dammer, U., Anselmetti, D., Dreier, M., Hegner, M., Huber, W., Hurst, J., Misevic, G. and Guntherodt, H.J. (1995b) In Forces in Scanning Probe Methods, Guntherodt, H.J., Ed.; Kluwer Academic Publishers:
Dordrecht, The Netherlands, pp 625.
Dammer, U., Hegner, M., Anselmetti, D., Wagner, P., Dreier, M., Huber, W. and Guntherodt, H.J. (1996). Specific antigen/antibody interactions measured by force microscopy. Biophys. J. 70: 2437-41.
Danon, D., Goldstein, L., Marikovsky, Y. and Skutelsky, E. (1972). Use of cationized ferritin as a label of negative charges on cell surfaces. J.
Ultrastruct. Res. 38: 500-10.
Davis, D.R. and Padlan, E.A. (1990). Antibody-antigen complexes. Annu.
Rev. Biochem. 59: 439-73.
Desmeules, P., Grandbois, M., Bondarenko, V.A., Yamazaki, A. and Salesse, C. (2002). Measurement of Membrane Binding between Recoverin, a Calcium-Myristoyl Switch Protein, and Lipid Bilayers by AFM-Based Force Spectroscopy. Biophys. J. 82: 3343-50.
Dettmann, W., Grandbois, M., Andre, S., Benoit, M., Wehle, A.K., Kaltner, H., Gabius, H.J. and Gaub, H.E. (2000). 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. Arch. Biochem. Biophys. 383: 157-70.
Dizhoor A.M., Ray, S., Kumar, S., Niemi, G., Spencer, M., Brolley, D., Walsh, K.A., Philipov, P.P., et al. (1991). Recoverin: a calcium sensitive activator of retinal rod guanylate cyclase. Science 22: 915-8.
Domke, J. and Radmacher, M. (1998). Measuring the elastic properties of thin polymer films with the atomic force microscope. Langmuir 14:
3320-5.
Ducker, W.A., Senden, T.J. and Pashley, R.M. (1991). Direct measurement of colloidal forces using an atomic force microscope. Nature 353: 239-41.
Ducker, W.A., Senden, T.J. and Pashley, R.M. (1992). Measurement of forces in liquids using a force microscope. Langmuir 8: 1831-6.
Evans, E., Berk, D. and Leung, A. (1991). Detachment of agglutinin-bonded red blood cells. Forces to rupture molecular-point attachments. Biophys.
J. 59: 838-48.
Evans, E., Ritchie, K. and Merkel, R. (1995). Sensitive force technique to probe molecular adhesion and structural linkages at biological interfaces. Biophys. J. 68: 2580-7.
Florin, E.L., Moy, V.T. and Gaub, H.E. (1994). Adhesion forces between individual ligand-receptor pairs. Science 264: 415-7.
Florin, E.-L., Rief, M., Lehmann, H., Ludwig, M., Dornmair, C., Moy, V. T.
and Gaub, H. E. (1995). Sensing specific molecular interactions with the atomic force microscope. Biosens. Bioelectron. 10: 895.
Frauenfelder, H., Sligar, S.G. and Wolynes, P.G. (1991). The energy landscapes and motions of proteins. Science 254:1598-1603.
Fritz, M., Radmacher, M., Petersen, N. and Gaub, H.E. (1994).
Visualization and identification of intracellular structures by force modulation microscopy and drug induced degradation. J. Vac. Sci.
Technol. B. 12: 1526-9.
Fritz, J., Anselmetti, D., Jarchow, J. and Fernandez-Busquets, X. (1997).
Probing single biomolecules with atomic force microscopy. J. Struct.
Biol. 119: 165-71.
Fritz, J., Katopodis, A.G., Kolbinger, F. and Anselmetti, D. (1998). Force-mediated kinetics of single P-selectin/ligand complexes observed by atomic force microscopy. Proc. Natl. Acad. Sci. USA 95: 12283-8.
Fritzsche, W. and Henderson, E. (1997). Mapping elasticity of rehydrated metaphase chromosomes by scanning force microscopy.
Ultramicroscopy 69: 191-200.
Fung, Y. C. (1993). “Biomechanics – Mechanical properties of living tissues.” , 2nd ed..Springer, New York.
Furuike, S., Ito, T. and Yamazaki, M. (2001). Mechanical unfolding of single filamin A (ABP-280) molecules detected by atomic force microscopy. FEBS Lett. 498: 72-5.
Guckenberger, R., Heim, M., Cevc, G., Knapp, H.F., Wiegrabe, W. and Hillebrand, A.(1994). Scanning tunneling microscopy of insulators and biological specimens based on lateral conductivity of ultrathin water films. Science 266: 1538-40.
Hansma, P.K., Drake, B., Marti, O., Gould, S.A.C. and Prater, C.B. (1989).
The scanning ion-conductance microscope. Science 243: 641-3.
Heinz, W.F. and Hoh, J.H. (1999a). Spatially resolved force spectroscopy of biological surfaces using the atomic force microscope. Trends Biotechnol. 17: 143-50.
Heinz, W.F. and Hoh, J.H. (1999b). Relative surface charge density mapping with the atomic force microscope. Biophys. J. 76: 528-38.
Hertadi, R. and Ikai, A. (2002). Unfolding mechanics of holo- and apocalmodulin studied by the atomic force microscope. Protein Sci. 11:
1532-8.
Hertz, H. (1882). Uber die Beruhrung fester elastischer Korper. J. Reine Angew. Mathematik 92: 156-71.
Hillier, A.C., Kim, S. and Bard, A.J. (1996). Measurement of double-layer forces at the electrode/electrolyte interface using the atomic force microscope: potential and anion dependent interactions. J. Phys. Chem.
100: 18808-17.
Hinterdorfer, P., Baumgartner, W., Gruber, H.J., Schilcher, K. and Schindler, H. (1996). Detection and localization of individual antibody-antigen recognition events by atomic force microscopy. Proc. Natl.
Acad. Sci. USA 93: 3477-81.
Hoh, J.H. and Schoenenberger, C.A. (1994). Surface morphology and mechanical properties of MDCK monolayers by atomic force microscopy. Biophys. J. 107: 1105-14.
Hutter, J.L. and Bechhoefer, J. (1994). Calibration of atomic force microscope tips. Rev. Sci. Instrum. 64: 1868-73.
Ishijima, Kojima, H., Higuchi, H., Harada, Y., Funatsu, T. and Yanagida, T.
(1996). Multiple- and single-molecule analysis of the actomyosin motor by nanometer-piconewton manipulation with a microneedle: unitary steps and forces. Biophys. J. 70: 383-400.
Israelachvili, J. and Adams, G. (1977). Measurement of forces between two mica surfaces in aqueous electrolyte solutions in the range 0-100 nm. J.
Chem. Soc. Faraday Trans. I. 74: 975-1000.
Israelachvili, J. (1992). Intermolecular and surface forces. Academic Press Limited, London. pp. 213-254.
Jaffe, L.F. and Nuccitelli, R. (1974). An ultrasensitive vibrating probe for measuring steady extracellular currents. J Cell Biol. 63: 614-28.
Kiridena, W., Jain, V., Kuo, P.K. and Liu, G.Y. (1997). Nanometer-scale Elasticity Measurements on Organic Monolayers Using Scanning Force Microscopy. Surf. Interface Anal. 25: 383-9.
Kuo, S. and Sheetz, M. (1993). Force of Single Kinesin Molecules Measured With Optical Tweezers. Science 260: 232-4.
Larson, I., Drummond, C.J., Chan, D.Y.C. and Grieser, F. (1997). Direct force measurements between silica and alumina. Langmuir 13: 2109-12.
Law, R., Carl, P., Harper, S., Dalhaimer, P., Speicher, D.W. and Discher, D.E. (2003). Cooperativity in forced unfolding of tandem spectrin repeats. Biophys. J. 84: 533-44.
Lee, G..U., Kidwell, D.A. and Colton, R.J. (1994a). Sensing Discrete Streptavidin-Biotin Interactions with Atomic Force Microscopy.
Langmuir 10: 354-7.
Lee, G.U., Chrisey, L.A. and Colton, R.J. (1994b). Direct measurement of the forces between complementary strands of DNA. Science 266: 771-3.
Lehenkari, P.P. and Horton, M.A. (1999). Single integrin molecule adhesion forces in intact cells measured by atomic force microscopy. Biochem.
Biophys. Res. Commun. 259: 645-50.
Ludwig, M., Dettmann, W. and Gaub, H.E. (1997). Atomic force microscope imaging contrast based on molecular recognition. Biophys.
J. 72:445-8.
Marshall, B.T., Long, M., Piper, J.W., Yago, T., McEver, R.P. and Zhu, C.
(2003). Direct observation of catch bonds involving cell-adhesion molecules. Nature 423: 190-3.
Marszalek, P.E., Lu, H., Li, H., Carrion-Vazquez, M., Oberhauser, A.F., Schulten, K. and Fernandez, J.M. (1999). Mechanical unfolding intermediates in titin modules. Nature 402: 100-3.
McEver, R.P., Moore, K.L. and Cummings, R.D. (1995). Leukocyte trafficking mediated by selectin-carbohydrate interactions. J. Biol.
Chem. 270: 11025-8.
McLaughlin, S. (1989). The electrostatic properties of membranes. Annu.
Rev. Biophys. Biophys. Chem. 18: 113-36.
Melander, W. and Horvath, C. (1977). Salt effect on hydrophobic interactions in precipitation and chromatography of proteins: an
interpretation of the lyotropic series. Arch. Biochem. Biophys. 183: 200-15.
Misevic, G.N., Finne, J. and Burger, M.M. (1987). Involvement of carbohydrates as multiple low affinity interaction sites in the self-association of the aggregation factor from the marine sponge Microciona prolifera. J. Biol. Chem. 262: 5870-80.
Mitsui, K., Hara, M. and Ikai, A. (1996). Mechanical unfolding of 2-macroglobulin molecules with atomic force microscope. FEBS Lett.
385: 29-33.
Miyata, H., Yasuda, R. and Kinosita, Jr. K. (1996). Strength and lifetime of the bond between actin and skeletal muscle alpha-actinin studied with an optical trapping technique. Biochim. Biophys. Acta. 1290: 83-8.
Mizes, H.A., Loh, K.G., Miller, R.J.D., Ahuja, S.K. and Grabowski, E.F.
(1991). Submicron probe of polymer adhesion with atomic force microscopy: Dependence on topography and material inhomogeneities.
Appl. Phys. Lett. 59: 2901-12.
Moller, C., Fotiadis, D., Suda, K., Engel, A., Kessler, M. and Muller, D.J.
(2003). Determining molecular forces that stabilize human aquaporin-1.
J. Struct. Biol. 142: 369-78.
Morris, V.J., Kirby, A.R. and Gunning, A.P. (1999). Atomic force microscopy for biologists. Imperial College Press, London, UK.
Moy, V.T., Florin, E.L. and Gaub, H.E. (1994a). Intermolecular forces and energies between ligands and receptors. Science 266: 257-9.
Moy, V.T., Florin, E.L. and Gaub, H.E. (1994b). Adhesive forces between ligand and receptor measured by AFM. Colloid Surf. A 93: 343-8.
Müller, D.J. and Engel, A. (1997). The height of biomolecules measured with the atomic force microscope depends on electrostatic interactions.
Biophys. J. 73: 1633-44.
Mueller, H., Butt, H.J. and Bamberg, E. (1999). Force measurements on myelin basic protein adsorbed to mica and lipid bilayer surfaces done with the atomic force microscope. Biophys. J. 76: 1072-9.
Nakajima, H., Kunioka, Y., Nakano, K., Shimizu, K., Seto., M. and Ando, T. (1997). Scanning force microscopy of the interaction events between a single molecule of heavy meromyosin and actin. Biochem. Biophys.
Research Communication 234: 178-82.
Nemes, C., Rozlosnik, N. and Ramsden, J.J. (1999).Direct measurement of the viscoelasticity of adsorbed protein layers using atomic force microscopy. Phys. Rev. E. Stat. Phys. Plasmas Fluids Relat. Interdiscip Topics. 60: 1166-9.
Nicklas, R. B. (1983). Measurements of the force produced by the mitotic spindle in anaphase. J. Cell Biol. 97: 542-8.
Oberhauser, A.F., Marszalek, P.E., Erickson, H.P. and Fernandez, J.M.
(1998). The molecular elasticity of the extracellular matrix protein tenascin. Nature 393: 181-5.
Oberhauser, A.F., Hansma, P.K., Carrion-Vazquez, M. and Fernandez, J.M.
(2001). Stepwise unfolding of titin under force-clamp atomic force microscopy. Proc. Natl. Acad. Sci. USA 98: 468-72.
Oroudjev, E., Soares, J., Arcdiacono, S., Thompson, J.B., Fossey, S.A. and Hansma, H.G. (2002). Segmented nanofibers of spider dragline silk:
atomic force microscopy and single-molecule force spectroscopy. Proc.
Natl. Acad. Sci. USA 99(Suppl 2): 6460-5.
Osada, T., Itoh, A. and Ikai, A. (2003). Mapping of the receptor-associated protein (RAP) binding proteins on living fibroblast cells using an atomic force microscope. Ultramicroscopy 97: 353-7.
Parsegian, V.A., Rand, R.P., Fuller, N.L. and Rau, D.C. (1986). Osmotic stress for the direct measurement of intermolecular forces. Methods Enzymol. 127: 400-16.
Pashley, R. M. (1981). DLVO and hydration forces between mica surfaces in Li, Na, K and Cs electrolyte solutions: a correlation of double-layer
Pashley, R. M. (1981). DLVO and hydration forces between mica surfaces in Li, Na, K and Cs electrolyte solutions: a correlation of double-layer