BIOTEC - Biotechnology Center TU Dresden

What drives cellular machines and how can we apply our knowledge?
Molecular interactions drive all processes in life. They determine the molecular crosstalk and build the basic language of biological processes. In water-soluble and membrane proteins molecular interactions fold the polypeptide into the functional protein, stabilize the structure, or lead to protein misfolding. These molecular forces determine protein-protein interactions, switching on and off ion channels, ligand-binding, the functional states of receptors, and the supramolecular assembly of molecular machines to functional units. Because of this enormous importance it is one pertinent demand in life sciences to characterize how these interactions drive biological processes and thus to decipher fundamentals of the biological language. To do so, we have pioneered two bionanotechnological methods, single-molecule atomic force microscopy (AFM) and single-molecule force spectroscopy (SMFS), which allows detecting inter- and intramolecular interactions of native membrane proteins. Recent extensions of both methods allow to image cells at nanometer resolution and to study interactions of single cells at molecular resolution using single-cell force spectroscopy (SCFS).

Learning to detect and interpret molecular forces and interactions

SMFS and SCFS allow detecting inter- and intramolecular forces directly correlated to the strength of biomolecular interactions. Both methods reveal intriguing insights into the strength of forces that stabilize biological structures, determine various biological interactions, and drive biological processes. Modifications in experimental setups allow precisely locating interactions occurring within the macromolecule. In most cases this feasibility could be demonstrated on membrane proteins by determining the stability of secondary structures of (non-)functional proteins. It could be investigated how their stabilizing interactions alter upon environmental changes such as caused by temperature, electrolyte or protein-protein interactions. Molecular interactions occurring upon ligand-binding thereby activating a transporter could be detected and located in the protein structure.

Cartoon showing the detection of molecular interactions of single living cells. The bionanotechnological technique CellHesionTM developed in the laboratory of cellular machines is now internationally sold as the standard lab equipment to characterize cellular adhesion down to the contribution of single molecules.

Originating from the experimental setup of the force spectroscopy it was thought that the interactions detected would be mostly of mechanical nature. However, it has become clear that force spectroscopy detects molecular interactions resulting from different physical and chemical origins. The ongoing challenge is to dissect and determine the extent to which various physical interactions contribute to a certain force detected in biological systems. For example, what are the life-times of these interactions? How do they contribute to ligand- and inhibitor-binding? How do these interactions follow each other thereby forming an interaction network? How does deleting or adding an interaction (e.g. by mutations) affect complex interaction networks of membrane proteins? Typically such questions are experimentally addressed using techniques from structural biology, where structural details help decipher the nature of theses interactions. Since these techniques only provide static pictures they are inherently limited in addressing these questions. Certainly, with the existing and the forthcoming generations of SMFS and SCFS it will be possible to characterize and understand the forest of interactions and their contributions in switching the functional state of cell membranes and membrane proteins.

Research and review articles

152. ‘New frontiers in atomic force microscopy: Analyzing interactions from single-molecules to cells’ D.J. Müller, M. Krieg, D. Alsteens & Y.F. Dufrene, Current Opinion in Biotechnology (2008) invited & submitted.

151. ‘A bond for a lifetime: Employing membrane nanotubes from living cells to determine receptor-ligand kinetics’ M. Krieg, J. Helenius, C.-P. Heisenberg & D.J. Müller, Angewandte Chemie International Edition (2008) in press.

150. ‘TPA primes a₂b₁ integrins for cell adhesion’ M. Tulla, J. Helenius, D.J. Müller & J. Heino, FEBS Letters (2008) in press.

149. ‘Narrow-band UVB induced externalization of selected nuclear antigens in keratinocytes: Implications for lupus erythematosus pathogenesis’ A. Reich, M. Meurer. A. Viehweg & D.J. Müller, Photochemistry and Photobiology (2008) in press.

148. ‘Surface morphology and mechanical properties of fibroblasts from scleroderma patients’ A. Reich, M. Meurer, B. Eckes, J. Friedrichs & D. J. Müller, Journal of Cellular and Molecular Medicine (2008) in press.

147. ‘AFM: A nanotool in membrane biology’ D.J. Müller, Biochemistry (2008) 47, 7986-7998.

146. ‘High-throughput single-molecule force spectroscopy for membrane proteins’ P.D Bosshart, F. Casagrande, P.L.T.M. Frederix, M. Ratera, C.A Bippes, D.J. Müller, M.l Palacin, A. Engel & D. Fotiadis, Nanotechnology (2008) 19, 384014.

145. ‘Fully automated single-molecule force spectroscopy for screening applications’ J. Struckmeier, R. Wahl, M. Leuschner, J. Nunes, H. Janovjak, U. Geisler, G. Hofmann, T. Jähnke & D.J. Müller, Nanotechnology (2008) 19, 384020.

144. ‘Transducer binding establishes localized interactions that tune sensory rhodopsin II’ D. Cisneros, L. Oberbarnscheidt, A. Pannier, J.P. Klare, J. Helenius, M. Engelhard, F. Oesterhelt & D.J. Müller, Structure (2008) 16, 1206-1213.

143. ‘Role of extracellular glutamic acids in the stability and energy landscape of bacteriorhodopsin’ K.T. Sapra, J. Doehner, V. Renugolpalkrishan, E. Padros & D.J. Müller, Biophysical Journal (2008) 95, 3407-3418.

142. ‘DNA annealing promotes a structural change in the Redb filament’ A. Erler, S. Wegmann, C. Elie-Caille, M. Maresca, R. Seidel, T. Heine, D.J. Müller & F. Stewart (2008) submitted.

141. ‘WNt/planar cell polarity dependent tissue epithelialization is required for left-right patterning’ P. Oteiza, M. Köppen, M. Krieg, S. Preibisch, D.J. Müller, M. Concha & C.P. Heisenberg (2008) submitted.

140. ‘Single-cell force spectroscopy’ J. Helenius, C.P. Heisenberg, H.E. Gaub & D.J. Müller, Journal of Cell Science (2008) 121, 1785-1791.

139. ‘Galectin-3 regulates the kinetics of integrin a₂b₁ mediated adhesion to collagen-I and -IV’ J. Friedrichs, A. Manninen, D.J. Müller & J. Helenius, Journal of Biological Chemistry (2008) in press.

138. ‘Single-cell force spectroscopy reveals β₁-integrin as a central molecule mediating adhesion of 32D-BCR-ABL cells to bone marrow stroma cells’ F.A. Fierro, A. Taubenberger, P.-H. Puech, G. Ehninger, M. Bornhäuser, D.J. Müller & T. Illmer, Journal of Molecular Biology (2008) 377, 1082-1093.

137. ‘Vertebrate membrane proteins: Structure, function and insights from biophysical approaches’ D.J. Müller, N. Wu & K. Palczewski, Pharmacological Reviews (2008) 60, 43-78.

136. ‘Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology’ D.J. Müller & Y. Dufrene, Nature Nanotechnology (2008) 3, 261-269. [Commentary ‘Still feeling the force’ Nature Nanotechnology (2008) 3, 241]

135. ‘Quantifying adhesive and tensile cell properties determining germ layer organization during gastrulation’ M. Krieg, Y. Arboleda, P.-H. Puech, J. Kaefer, F. Graener, D.J. Müller & C.P. Heisenberg, Nature Cell Biology (2008) 10, 429-436. (incl. front cover) [Commentary by J. B. A. Green ‘Sophistication of cell sorting’ Nature Cell Biology (2008) 10, 375-377]

134. ‘Strategies to prepare and characterize native protein membranes by AFM’ D.J. Müller & A. Engel, Current Opinion in Colloid and Interface Science (2008) 13, 338-350.

133. ‘Observing fibrillar assemblies on scrapie-infected cells’ S. Wegmann, M. Miesbauer, K.F. Winklhofer, J. Tatzelt & D.J. Müller, Pflügers Archiv - European Journal of Physiology (2008) 456, 83-93.

132. ‘From valleys to ridges: Exploring the energy landscape of single membrane proteins’ H. Janovjak, K.T. Sapra, A. Kedrov & D.J. Müller, ChemPhysChem (2008) 9, 954-956.

131. ‘An intermediate step in the evolution of ATPases - a hybrid F_O-V_O rotor in a bacterial Na⁺ F₁F_O ATP synthase’ M. Fritz, A.L. Klyszejko, N. Morgner, J. Vonck, B. Brutschy, D.J. Müller, Th. Meier & V. Müller, FEBS Journal (2008) 275, 1999-2007. (incl. front cover)

130. ‘Folding and assembly of proteorhodopsin’ A.L. Klyszejko, S. Shastri, S.A. Mari, D.J. Müller & C. Glaubitz, Journal of Molecular Biology (2008) 376, 35-41. (incl. front cover)

129. ‘Mechanical properties of bovine rhodopsin and bacteriorhodopsin dictate energy landscape and guide conformational changes’ K.T. Sapra, P.S.-H. Park, K. Palczewski & D.J. Müller, Langmuir (2008) 24, 1330-1337.

128. ‘Point mutations of membrane protein alter energy landscape and unfolding pathways’ K.T. Sapra, P. Balasubramanian, D. Labudde, J. Bowie & D.J. Müller, Journal of Molecular Biology (2008) 376, 1076-1090.

127. ‘Examining the dynamic energy landscape of an antiporter upon inhibitor binding’ A. Kedrov, M. Appel, H. Baumann, Ch. Ziegler & D.J. Müller, Journal of Molecular Biology (2008) 375, 1258-1266.

126. ‘Single-molecule microscopy and force spectroscopy of membrane proteins’ A. Engel, H. Janovjak, D. Fotiadis, A. Kedrov, D. Cisneros & D.J. Müller in ‘Single molecules and Nanotechnology’ eds R. Rigler & H. Vogel, (2007) Springer Heidelberg, Germany.

125. ‘Straight GDP-tubulin protofilaments form in the presence of taxol’ C. Elie-Caille, F. Severin, J. Helenius, J. Howard, D.J. Müller & A.A. Hyman, Current Biology (2007) 20, 1765-1770. (incl. front cover)

124. ‘Atomic force microscopy and spectroscopy of native membrane proteins’ D.J. Müller & A. Engel, Nature Protocols (2007) 2, 2191-2197.

123. ‘Studying integrin-mediated cell adhesion on the single-molecule level by using AFM force spectroscopy’ C.M. Franz, A. Taubenberger, P.-H. Puech & D.J. Müller, Science STKE (2007) 406, pl5.

122. ‘Structural alterations provoked by narrow band ultraviolet B in immortalized keratinocytes: Assessment by atomic force microscopy’ A. Reich, B. Lehmann, M. Meurer & D.J. Müller, Experimental Dermatology (2007) 16, 1007-1015. (incl. front cover)

121. ‘The oligomeric state of c rings from cyanobacterial F-ATP synthases varies from 13 to 15’ D. Pogoryelov, C. Reichen, A. Klyszejko, R. Brunisholz, D.J. Müller, P. Dimroth & Th. Meier, Journal of Bacteriology (2007) 189, 5895-5902. (incl. front cover)

120. ‘Free energy of membrane protein unfolding derived from single-molecule force measurements’ J. Preiner, H. Janovjak, C. Rankl, H. Knaus, D.A. Cisneros, A. Kedrov, F. Kienberger, D.J. Müller & P. Hinterdorfer, Biophysical Journal (2007) 93, 930-937.

119. ‘Galectin-3 and galectin-9 contribute to adhesion and cystogenesis in epithelial MDCK cells’ J. Friedrichs, J. Torkko, J. Helenius, J. Füllekrug, D.J. Müller, K. Simons & A. Manninen, Journal of Biological Chemistry (2007) 282, 29375-29383.

118. ‘Cellular remodelling of individual collagen fibrils visualized by time-lapse AFM’ J. Friedrichs, A. Taubenberger, C.M. Franz & D.J. Müller, Journal of Molecular Biology (2007) 372, 594-607. (incl. front cover)

117. ’Stabilizing effect of Zn²⁺ in native bovine rhodopsin’ P.S.-H. Park, K.T. Sapra, M. Koliński, S. Filipek, K. Palczewski & D.J. Müller, Journal of Biological Chemistry (2007) 282, 11377-11385.

116. ‘Transmembrane helices have rough energy surfaces’ H. Janovjak, H. Knaus & D.J. Müller, Journal of the American Chemical Society (2007) 129, 246-247.

115. ‘Development of nanoscopic collagen matrices for biological and biotechnological applications’ D.A. Cisneros, J. Friedrichs, A. Taubenberger, C. Franz & D.J. Müller, SMALL (2007) 3, 956-963.

114. ‘Revealing early steps of a₂b₁ integrin-mediated adhesions to collagen type I using single-cell force spectroscopy’ A. Taubenberger, D.A. Cisneros, J. Friedrichs, P.-H. Puech, D.J. Müller & C.M. Franz, Molecular Biology of the Cell (2007) 18, 1634-1644.

113. ‘Aminosulfonate modulated pH induced conformational changes in Connexin26 hemichannels’ J. Yu, Ch. Bippes. G. Hand, D.J. Müller & G. Sosinsky, Journal of Biological Chemistry (2007) 282, 8895-8904. (incl. front cover)

112. ‘Detecting molecular interactions that stabilize, activate and guide ligand-binding of the sodium/proton antiporter MjNhaP1 from Methanococcus jannaschii’ A. Kedrov, S. Wegmann, S. Smiths, P. Goswami, H. Baumann, & D.J. Müller, Journal of Structural Biology (2007) 159, 290-301.

111. ‘Digital force-feedback for protein unfolding experiments using atomic force microscopy’ Ch. Bippes, H. Janovjak, A. Kedrov & D.J. Müller, Nanotechnology (2007) 18, 1-7. doi:10.1088/0957-4484/18/4/044022

110. ‘Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy’ A. Kedrov, H. Janovjak, K.T. Sapra & D.J. Müller, Annual Review of Biophysics and Biomolecular Structure (2007) 36, 233-260.

109. ‘A novel pattern recognition algorithm to classify membrane protein unfolding pathways with high-throughput single molecule force spectroscopy’ A. Marisco, D. Labudde, T. Sapra, D.J. Müller & M. Schröder, Bioinformatics (2007) 23, e231-236.

108. ‘Out and in: Simplifying membrane protein studies by AFM’ D.J. Müller, Biophysical Journal (2006) 91, 3133-3134.

107. ‘Imaging and detecting molecular interactions of single transmembrane proteins’ H. Janovjak, A. Kedrov, D.A. Cisneros, K.T. Sapra, J. Struckmeier & D.J. Müller, Neurobiology of Aging (2006) 27, 546-561.

106. ‘Characterizing folding, structure, molecular interactions and ligand gated activation of single sodium/proton antiporters’ A. Kedrov & D.J. Müller, Naunyn-Schmiedeberg’s Archives of Pharmacology (2006) 372, 400-412.

105. ‘Hochauflösende Rasterkraftmikroskopie mikrobieller Membranen’ D.J. Müller, Biospektrum (2006) 12, 483-485.

104. ‘Structure of the rhodopsin dimer: A working model for G-protein coupled receptors’ D. Fotiadis, B. Jastrzebska, A. Philippsen, D.J. Müller, K. Palczewski & A. Engel, Current Opinion in Structural Biology (2006) 16, 252-259.

103. ‘Single-molecule studies of membrane proteins’ D.J. Müller, K.T. Sapra, S. Scheuring, A. Kedrov, P.L. Frederix, D. Fotiadis, & A. Engel, Current Opinion in Structural Biology (2006) 16, 489-495.

102. ‘Differentiating ligand and inhibitor interactions of a single antiporter’ A. Kedrov, Ch. Ziegler & D.J. Müller, Journal of Molecular Biology (2006) 362, 925-932.

101. ‘A new approach to prepare membrane proteins for single molecule AFM imaging’ D.A. Cisneros, D.J. Müller, S.M. Daud & J.H. Lakey, Angewandte Chemie International Edition (2006) 45, 3252-3256.

100. ‘Analysis assistant for single-molecule force spectroscopy data on membrane proteins - MPTV’ F. Müller, D.J. Müller & D. Labudde, Bioinformatics (2006) 22, 1796-1799.

99. ‘Detecting molecular interactions that stabilize native bovine rhodopsin’ T. Sapra, P.S.H. Park, A. Engel, S. Filipek, D.J. Müller & K. Palzcewski, Journal of Molecular Biology (2006) 358, 255-269.

98. ‘Observing growth steps of collagen self-assembly by time-lapse high-resolution atomic force microscopy’ D.A. Cisneros, C. Hung, C.M. Franz & D.J. Müller, Journal of Structural Biology (2006) 154, 232-245.

97. ‘Rastersondenmikroskopie’ in Lehrbuch ‘Bioanalytik’ Herausgeber Lottspeich/Engels, 2. Edition, Spektrum Akademischer Verlag, Heidelberg (2006).

96. ‘Bacteriorhodopsin folds into the membrane against an external force’ M. Kessler, K. Gottschalk, H. Janovjak, D.J. Müller & H.E. Gaub, Journal of Molecular Biology (2006) 357, 644-654.

95. ‘A new technical approach to quantify cell adhesion forces by AFM’ P.-H.Puech, K. Poole, D. Knebel & D.J. Müller, Ultramicroscopy (2006) 106, 637-644.

94. ‘Characterizing molecular interactions in different bacteriorhodopsin assemblies by single-molecule force spectroscopy’ T. Sapra, H. Besir, D. Oesterhelt & D.J. Müller, Journal of Molecular Biology (2006) 355, 640-650.

93. ‘Direct measurement of single-molecule visco-elasticity in AFM force-extension measurements’ Ch. Bippes, A. Humphris, D.J. Müller & H. Janovjak, European Biophysical Journal (2006) 35, 287-292.

92. ‘Observing folding pathways and kinetics of a single membrane protein’ A. Kedrov, H. Janovjak, Ch. Ziegler, W. Kühlbrandt & D.J. Müller, Journal of Molecular Biology (2006) 355, 2-8.

91. ‘Zusammenhänge zwischen Oberflächenstruktur und funktionellem Zustand der Zellmembran von Krebszellen’ K. Poole & D.J. Müller, Biospektrum (2005) 4, 465-466.

90. ‘Atomic force microscopy’ H. Janovjak, R. Sahwney, M. Stark & D.J. Müller in ‘Techniques in Microscopy for Biomedical Applications’, World Scientific Press, Singapore (2005). ISBN: 9812564349

89. ‘Pattern recognition of single-molecule force spectroscopy data’ M. Kuhn, H. Janovjak, M. Hubain, D. Labudde & D.J. Müller, Biophotonics International (2005) 12(8), 50-51.

88. ‘Microbial surfaces investigated by atomic force microscopy’ Y. Dufrene & D.J. Müller, Methods in Microbiology (2005) 34, 163-197.

87. ‘Force microscopy and spectroscopy from single membrane proteins to entire cells’ K. Poole & D.J. Müller, Imaging & Microscopy (2005) 3, 39-41.

86. ‘Wnt11 functions in gastrulation by controlling cell cohesion through Rab5c and E-cadherin’ F. Ulrich, M. Krieg, E. Schötz, V. Link, I. Castanton, A. Taubenberger, D.J. Müller, P.-H. Puech & C.P. Heisenberg, Developmental Cell (2005) 9, 555-564.

85. ‘Analysing focal adhesion structure by AFM‘ C. Franz & D.J. Müller, Journal of Cell Science (2005) 118, 5315-5323. [Commentary by J. Bradbury ‘Taking the lid of focal adhesions’ Journal of Cell Science (2005) 118, e2104]

84. ‘Structural evidence for a constant c₁₁ ring stoichiometry in the sodium F-ATP synthase’ Th. Meier, J. Yu, Th. Raschle, F. Henzen, P. Dimroth & D.J. Müller, FEBS Journal (2005) 272, 5474-5483.

83. ‘The c15 ring of the Spirulina platensis F-ATP synthase: F₁/F_o symmetry mismatch is not obligatory’ D. Pogoryelov, J. Yu, Th. Meier, J. Vonck, P. Dimroth & D.J. Müller, Embo reports (2005) 6, 1040-1044.

82. ‘Measuring cell adhesion forces of primary gastrulating cells from zebrafish using atomic force microscopy’ P.-H. Puech, A. Taubenberger, F. Ulrich, M. Krieg, D.J. Müller & C.P. Heisenberg, Journal of Cell Science (2005) 118, 4199-4206.

81. ‘Locating ligand binding and activation of a single antiporter’ A. Kedrov, M. Krieg, Ch. Ziegler, W. Kühlbrandt & D.J. Müller, Embo reports (2005) 6, 668-674.

80. ‘Complex stability of single proteins explored by forced unfolding experiments’ H. Janovjak, T. Sapra & D.J. Müller, Biophysical Journal (2005) 88, L37-L39.

79. ‘Flexible, actin-based ridges co-localize with the beta1 integrin on the surface of melanoma cells’ K. Poole & D.J. Müller, British Journal of Cancer (2005) 92, 1499-1505.

78. ‘Automated alignment and pattern recognition of single-molecule force spectroscopy data’ M. Kuhn, H. Janovjak, M. Hubain & D.J. Müller, Journal of Microscopy (2005) 218, 125-132.

77. ‘Probing different origins of potential barriers stabilizing the membrane proteins halorhodopsin and bacteriorhodopsin’ D. Cisneros, D. Oesterhelt & D.J. Müller, Structure (2005) 13, 235-242. [Commentary by G. Chin ‘Deconstructing membrane proteins’ Science (2005) 307, 1172]

76. ‘Dynamic response of single bacteriorhodopsins, determined by single-molecule force modulation spectroscopy’ H. Janovjak, D.J. Müller & A. Humphris, Biophysical Journal (2005) 88, 1423-1431. [Commentary by J. van Noort ‘Unravelling bacteriorhodopsin’ Biophysical Journal (2005) 88, 763-764]

75. ‘Extended range of force loading rates for AFM single-molecule experiments’ H. Janovjak, J. Struckmeier & D.J. Müller, European Biophysical Journal (2005) 34, 91-96.

74. ‘Molecular-scale topographic cues induce the orientation and directional movement of fibroblasts on two-dimensional collagen surfaces’ K. Poole, K. Khairy, J. Friedrichs, C. Franz, D. Cisneros, J. Howard & D.J. Müller, Journal of Molecular Biology (2005) 349, 380-386.

73. ‘Cell surface ridges characterized by advanced light and atomic force microscopy’ A. Sharma, K. Anderson & D.J. Müller, FEBS Letters (2005) 579, 2001-2008.

72. ‘Atomic force microscopy of biological samples’ P. Frederix, B.W. Hoogenboom, D. Fotiadis, D.J. Müller & A. Engel, MRS Bulletin (2004) 29, 449-455. (incl. front cover).

71. ‘Assembly of collagen into microribbons: effects of pH and electrolytes’ F. Jiang, H. Hörber, J. Howard & D.J. Müller, Journal of Structural Biology (2004) 148, 268-278. (incl. front cover).

70. ‘The effect of raft lipid depletion on microvilli formation in MDCK cells, visualized by atomic force microscopy‘ K. Poole, D. Meder, K. Simons & D.J. Müller, FEBS Letters (2004) 565, 53-58. (incl. front cover).

69. ‘Creating nanoscopic collagen matrices using atomic force microscopy’ F. Jiang, K. Khairy, K. Poole, J. Howard & D.J. Müller, Microscopy Research Technique (2004) 64, 435-440.

68. ‘Probing the energy landscape of the membrane protein bacteriorhodopsin’ H. Janovjak, J. Struckmeier, M. Hubain, A. Kedrov, M. Kessler & D.J. Müller, Structure (2004) 12, 871-879. (incl. front cover).

67. ‘Controlled unfolding and refolding of a single sodium-proton antiporter’ A. Kedrov, Ch. Ziegler, H. Janovjak, W. Kühlbrandt & D.J. Müller, Journal of Molecular Biology (2004) 340, 1143-1152.

66. ‘Atomic force bio-analytics’ P. Frederix, T. Akiyama, U. Staufer, Ch. Gerber, D. Fotiadis, D.J. Müller & A. Engel, Current Opinion in Chemical Biology (2003) 7, 641-647.

65. ‘Fourteen protomers compose the oligomer III of the proton-rotor in spinach chloroplast ATP-synthase’ H. Seelert, N. Dencher & D.J. Müller, Journal of Molecular Biology (2003) 333, 374-344. (incl. front cover).

64. ‘Temperature dependent unfolding of bacteriorhodopsin’ H. Janovjak, M. Kessler, D. Oesterhelt, H. Gaub & D.J. Müller, EMBO Journal (2003) 22, 5220-5229.

63. ‘Observing the growth of individual actin filaments in cell extracts by time-lapse atomic force microscopy’ T. Lehto, M. Miaczynska, M. Zerial, D.J. Müller & F. Severin, FEBS Letters (2003) 551, 25-28. (incl. front cover).

62. ‘Determining molecular forces that stabilize human aquaporin-1’ C. Moeller, D. Fotiadis, K. Suda, A. Engel, M. Kessler & D.J. Müller, Journal of Structural Biology (2003) 142, 369-378. (incl. front cover). [Selected as Paper of the year from Journal of Structural Biology]

61. ‘Observing membrane protein diffusion at subnanometer resolution’ D. J. Müller, A. Engel, Th. Meier, U. Matthey, P. Dimroth & K. Suda, Journal of Molecular Biology (2003) 327, 925-930.

60. ‘Controlled nanomanipulation of biological specimens with the atomic force microscope’ D. Fotiadis, S. Scheuring, S.A. Müller, A. Engel & D.J. Müller, Micron (2002) 33, 385-397. (incl. front cover).

59. 'Conformations, flexibility, and interactions observed on individual membrane proteins by atomic force microscopy ' D.J. Müller & A. Engel, Methods in Cell Biology (2002) 68, 257-299.

58. ‘Observing structure function and assembly of single proteins by AFM’ D.J. Müller, H. Janovjak, T. Lehto, L. Kuerschner & K. Anderson, Progress in Biophysics and Molecular Biology (2002) 71, 1-43.

57. ‘Biomolecular imaging using atomic force microscopy’ D.J. Müller & K. Anderson, Trends in Biotechnology (2002) 20, S45-S49.

56. ‘Sampling effects influence the heights measured with atomic force microscopy’ J.B. Heymann, C. Moeller & D.J. Müller, Journal of Microscopy (2002) 205,43-51.

55. ‘Stability of bacteriorhodopsin a-helices and loops analyzed by single molecule force spectroscopy’ D.J. Müller, M. Kessler, F. Oesterhelt, C. Moeller, D. Oesterhelt & H. Gaub, Biophysical Journal (2002) 83, 3578-3588.

54. ‘Conformational changes in surface structures of isolated Connexin26 gap junctions’ D.J. Müller, G.M. Hand, A. Engel & G.E. Sosinsky, EMBO Journal (2002) 21, 3598-3607.

53. ‘Identification and structure of a putative Ca²⁺-binding domain at the C terminus of AQP1’ D. Fotiadis, K. Suda, P. Tittmann, P. Jenö, A. Philippsen, D.J. Müller, H. Gross & A. Engel, Journal of Molecular Biology (2002) 318, 1381-1394.

52. ‘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. Müller, Biophysical Journal (2002) 82, 1667-1676. (incl. front cover).

51. ‘Sampling the conformational space of membrane protein surfaces with the AFM’ S. Scheuring, D.J. Müller, H. Stahlberg, H.-A. Engel & A. Engel, European Biophysical Journal (2002) 31, 172-178.

50. ‘Isolation and characterization of gap junctions from tissue culture cells’ G.M. Hand, D.J. Müller, B. Nicholson, A. Engel & G.E. Sosinsky, Journal of Molecular Biology (2002) 315, 587-599.

49. ‘Single proteins observed by atomic force microscopy’ S. Scheuring, D. Fotiadis, C. Möller, S. Müller, A. Engel & D.J. Müller, Single Molecule (2001) 2, 59-67.

48. ‘The central plug in the reconstituted undecameric c cylinder of a bacterial ATP synthase consists of phospholipids’ Th. Meier, U. Matthey, F. Henzen, P. Dimroth, & D.J. Müller, FEBS Letters (2001) 505, 353-356. (incl. front cover).

47. ‘Subunits constrain stoichiometry of ATP synthase rotor’ D.J. Müller, N. Dencher, Th. Meier, P. Dimroth, H. Stahlberg, K. Suda, A. Engel, H. Seelert & U. Matthey, FEBS Letters (2001) 504, 219-222.

46. 'Bacterial sodium ATP synthase has an undecameric motor' H. Stahlberg, D.J. Müller, K. Suda, D. Fotiadis, A. Engel, Th. Meier, U. Matthey & P. Dimroth, EMBO Reports (2001) 2, 229-233. (incl. front cover).

45. ‘From images to interactions: High-resolution phase imaging in tapping-mode atomic force microscopy’ M. Stark, C. Möller, D.J. Müller & R. Guckenberger, Biophysical Journal (2001) 80, 3009-3018.

44. ‘Observing proteins at work with the atomic force microscope’ A. Engel & D.J. Müller, Nature Structural Biology (2000) 7, 715-718. (incl. front cover).

43. 'Reversible loss of crystallinity during photobleaching purple membrane' C. Möller, G. Büldt, N.A. Dencher, A. Engel & D.J. Müller, Journal of Molecular Biology (2000) 301, 869-879.

42. 'The surface topography of lens MIP supports dual functions' D. Fotiadis, L. Hasler, D.J. Müller, H. Stahlberg, J. Kistler & A. Engel, Journal of Molecular Biology (2000) 300, 779-789. (incl. front cover).

41. 'Atomic force microscopy of native purple membrane' D.J. Müller, J.B. Heymann, F. Oesterhelt, C. Möller, H. Gaub, G. Büldt & A. Engel, Biochemical Biophysical Acta (2000) 1460, 27-38.

40. ‘Conformational changes, flexibilities and intramolecular forces observed on individual proteins using AFM' D.J. Müller, D. Fotiadis, C. Möller, S. Scheuring & A. Engel, Single Molecule (2000) 1, 115-118.

39. 'Conformations of the rhodopsin third cytoplasmic loop grafted onto bacteriorhodopsin' J.B. Heymann, M. Pfeiffer, V. Hildebrandt, D. Fotiadis, B. de Groot, R. Kabak, A. Engel, D. Oesterhelt & D.J. Müller, Structure (2000) 8, 643-653.

38. 'Proton powered turbine of a plant motor’ H. Seelert, A. Poetsch, N. Dencher, A. Engel, H. Stahlberg & D.J. Müller, Nature (2000) 405, 418-419.

37. 'Unfolding pathways of individual bacteriorhodopsins' F. Oesterhelt, D. Oesterhelt, M. Pfeiffer, A. Engel, H. Gaub & D.J. Müller, Science (2000) 288, 143-146. [Commentary by J.G. Forbes & G.H. Lorimer ‘Unravelling a membrane protein’ Science (2000) 288, 63-64]

36. 'Atomic force microscopy: a powerful tool to observe biomolecules at work' A. Engel, Y. Lyubchenko & D.J. Müller, Trends in Cell Biology (1999) 9, 77-80.

35. 'Atomic force microscopy: a forceful way with single molecules' A. Engel, H. Gaub & D.J. Müller, Current Biology (1999) 9, R133-R136.

34. 'Sample preparation techniques in scanning probe microscopy' M. Amrein & D.J. Müller, Nanobiology (1999) 4, 229-256.

33. Charting the surfaces of purple membrane' J.B. Heymann, D.J. Müller, E. Landau, J. Rosenbusch, E. Pebay-Peroulla, G. Büldt & A. Engel, Journal of Structural Biology (1999) 128, 243-249. (incl. front cover).

32. 'Controlled unzipping of a bacterial surface layer with atomic force microscopy' D.J. Müller, W. Baumeister & A. Engel, Proc. Natl. Acad. Sci. USA (1999) 96, 13170-13174.

31. 'High resolution topographs of the Escherichia coli waterchannel aquaporin Z' S. Scheuring, P. Ringler, M. Borgina, H. Stahlberg, D.J. Müller, P. Agre & A. Engel, EMBO Journal (1999) 18, 4981-4987. (incl. front cover).

30. 'Tapping mode atomic force microscopy produces faithful high-resolution images of protein surfaces' C. Möller, M. Allen, V. Elings, A. Engel & D.J. Müller, Biophysical Journal (1999) 77, 1150-1158.

29. 'Surface structures of native bacteriorhodopsin depend on the molecular packing arrangement in the membrane' D.J. Müller, H.-J. Sass, S.A. Müller, G. Büldt & A. Engel, Journal of Molecular Biology (1999) 285, 1903-1909.

28. 'pH and voltage induced structural changes of porin OmpF explains channel closure' D.J. Müller & A. Engel, Journal of Molecular Biology (1999) 285, 1347-1351.

27. 'Electrostatically balanced subnanometer imaging of biological specimens by atomic force microscope' D.J. Müller, D. Fotiadis, S. Scheuring, S.A. Müller & A. Engel, Biophysical Journal (1999) 76, 1101-1111.

26. 'Imaging streptavidin 2D crystals on biotinylated lipid monolayers at high resolution with the atomic force microscope' S. Scheuring, D.J. Müller, P. Ringler, B. Heyman & A. Engel, Journal of Microscopy (1999) 193, 28-33.

25. 'Non-specular reflectivity of spin flipped neutrons' Th. Krist, D.J. Müller & F. Mezei, Physica B (1999) 267-268,194-197.

24. 'Preparation and observation of purple membranes by AFM‘ D.J. Müller, G. Büldt & A. Engel in Procedures in Scanning Probe Microscopies ed by. Colton, Engel, Frommer, Gaub, Gewirth, Guckenberger, Heckl, Parkinson, Rabe (1998), 425-427.

23. '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. Jenö, H. Gross & A. Engel, Journal of Molecular Biology (1998) 283, 83-94.

22. 'Mapping flexible protein domains at subnanometer resolution with the AFM' D.J. Müller, D. Fotiadis & A. Engel, FEBS Letters (1998) 430, 105-111. (incl. front cover).

21. 'Atomic force microscopy provides molecular details of cell surfaces' C.-A. Schoenenberger, D.J. Müller & A. Engel, in Modern optics, electronics and high precision technqiues in cell biology (1997), ed. G. Isenberg, Springer Verlag, Heidelberg. 1-33. (incl. front cover).

20. 'Preparation techniques for the observation of native biological systems with the atomic force microscope' D.J. Müller, A. Engel & M. Amrein, Biosensors & Bioelectronics (1997) 8, 867-877.

19. 'High-resolution imaging of native biological sample surfaces with scanning probe microscope' A. Engel, C.-A. Schoenenberger & D.J. Müller, Current Opinion in Structural Biology (1997) 7, 279-284.

18. 'Electron and atomic force microscopy of membrane proteins' J.B. Heymann, D.J. Müller, K. Mitsuoka & A. Engel, Current Opinion in Structural Biology (1997) 7, 543-549 (incl. front cover).

17. 'Structural changes of native membrane proteins monitored at subnanometer resolution with the atomic force microscope' D.J. Müller, C.-A. Schoenenberger, F. Schabert & A. Engel, Journal of Structural Biology (1997) 119, 149-157.

16. 'The height of biomolecules measured with the atomic force microscope depends on electrostatic interactions' D.J. Müller & A. Engel, Biophysical Journal (1997) 73,1633-1644.

15. 'Adsorption of biological molecules to a solid support for scanning probe microscopy' D.J. Müller, M. Amrein & A. Engel, Journal of Structural Biology (1997) 119, 172-188. (incl. front cover).

14. 'The bacteriophage ø29 head-tail connector imaged at high resolution with atomic force microscopy' D.J. Müller, A. Engel, J.L.Carrascosa & M. Velez, EMBO Journal (1997) 16, 101-107. (incl. front cover).

13. 'Interface Effects in FeCo-Si Multilayers' D.J. Müller, Th. Krist, P. Schubert-Bischoff & F. Mezei, Physica B (1997) 234-236, 1050-1051.

12. 'Structural inhomogeneity and biochemical properties of articular cartilage' J.S. Jurvelin, J.P.A. Arokoski, D.J. Müller, H.J. Helminen & E.B. Hunziker, Medical and Biological Engineering & Computing (1996) 34, 321-322.

11. 'Immuno atomic force microscopy of purple membranes' D.J. Müller, C.-A. Schoenenberger, G. Büldt & A. Engel, Biophysical Journal (1996) 68, 1681-1686.

10. 'Surface and sub-surface morphology of bovine humeral articular cartilage as assessed by atomic force- and transmission electron microscopy' J.S. Jurvelin, D.J. Müller, M. Wong, D. Studer, A. Engel & E.B. Hunziker, Journal of Structural Biology (1996) 117, 45-54.

9. 'Conformational change of the hexagonally packed intermediate layer of Deinococcus radiodurans observed with atomic force microscopy' D.J. Müller, W. Baumeister & A. Engel, Journal of Bacteriology (1996) 178, 3325-3329.

8. 'Surface topographies at subnanometer-resolution reveal asymetry and sidedness of aquaporin-1' T. Walz, P. Tittmann, K.H. Fuchs, D.J. Müller, B.L. Smith, P. Agree, H. Gross & A. Engel, Journal of Molecular Biology (1996) 264, 907-918.

7. 'Abbildung und Manipulation biologischer Makromoleküle im Sub-Nanometer Bereich' D.J. Müller & A. Engel, Biospektrum (1995) 4, 30-31. (incl. front cover).

6. 'Imaging purple membranes in aqueous solutions at sub-nanometer resolution by atomic force microscopy' D.J. Müller, F.A. Schabert, G. Büldt & A. Engel, Biophysical Journal (1995) 68, 1681-1686.

5. 'The use of MoTe2 as a substrate for the imaging of biological molecules during scanning tunneling microscopy' S.A. Campbell, D.J. Müller, H. Jungblut, M. Giersig, Y. Tomm & H.J. Lewerenz, Analyst (1994) 119, 727-734.

4. 'Scanning tunneling microscopy observation of atomic structures on Silicon (100) surface in air' H. Jungblut, D.J. Müller, M. Aggour & H.J. Lewerenz, Electrochemica Acta (1993) 38, 1367-1371.

3. 'Bonding of biomolecules to surfaces: scanning tunneling microscopy with group VI layered substrates' H. Jungblut, H.J. Lewerenz, D.J. Müller & S.A. Campbell, Applied Physics Communications (1992) 11, 31-40.

2. 'Direct observation of reverse transcriptases by scanning tunneling microscopy' H.J. Lewerenz, H. Jungblut, S.A. Campbell, M. Giersig & D.J. Müller, Journal of Aids Research and Human Retroviruses (1992) 8, 1663-1666.

1. 'Scanning tunneling microscopy observation of biomolecules on layered materials' H. Jungblut, S.A. Campbell, M. Giersig, D.J. Müller & H.J. Lewerenz, Faraday Discussions (1992) 94,183-197.

Articles of research group “cellular machines” (published without D.J. Müller)

6. ‘Self-assembling layers created by membrane proteins on gold’ D.S. Shah DS, M.B. Thomas, S. Phillips, D.A. Cisneros, A.P. Le Brun, S.A. Holt, J.H. Lakey, Biochemical Society Transaction (2007) 35, 522-526.

5. ‘Pulling single bacteriorhodopsin out of a membrane: Comparison of simulation and experiment’ M. Cieplak, S. Filipek, H. Janovjak, K.A. Krzyśko, Biochimical Biophysical Acta (2006) 1758, 537-544.

4. ‘Huntingtin-HAP40 complex is a novel Rab5 effector that regulates early endosome motility and is upregulated in Huntington disease’ A. Pal, F. Severin, B. Lommer, A. Shevchenko, M. Zerial, Journal of Biological Chemistry (2006) 172, 605-618.

3. ‘Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B’ S. Hoepfner, F. Severin, A. Cabezas, B. Habermann, A. Runge, D. Gillooly, H. Stenmark & M. Zerial, CELL (2005) 121, 437-450.

2. 'Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast' A. Pozniakovsky, D. Knorre, Ol. Markova, A Hyman, V. Skulachev & F. Severin, Journal of Biological Chemistry (2005) 168, 257-269.

1. 'CLASP1 and CLASP2 bind to EB1 and regulate microtubule plus end dynamics at the cell cortex' Y. Mimori-Kiyosue, I. Grigoriev, G. Lansbergen, H. Sasaki, C. Matsui, F. Severin, N. Galjart, F. Grosveld, I. Vorobiev, S. Tsukit & A. Akhmanova, Journal of Cell Biology (2005) 168, 141-153.

You can find a list of current group members here.