Daniel Müller has been a full Professor of Biophysics at the ETH Zurich since 1. April 2010. Prof. Müller was born on March 22, 1965 in Bad Wimpfen, Germany and studied physics at the University of Technology of Berlin and the Hahn-Meitner-Institute in Berlin, Germany. After finishing his studies he started his Ph.D. in Biophysics at the Forschungszentrum Jülich, Germany, with Georg Büldt and at the Biozentrum Basel, Switzerland with Andreas Engel. In 1997 he finished his Ph.D. and received the Prize for the best Ph.D. thesis in Life Sciences of the University of Basel. In 2000 Daniel Müller received his habilitation ‘venia legendi’ in Biophysics from the University of Basel. In 2000 Daniel Müller continued his career as a group leader at the newly founded Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany. In 2002 Daniel Müller accepted a full professorship of Cellular Machines at the Biotechnology Center of the University of Technology, Dresden. He acted as a director of the Center from 2003-2005. In 2006 Müller co-funded one of the largest Bionanotechnology Spin-Offs in Germany. The company developing and manufacturing the world’s first robot that fully automatically conducts single-molecule experiments was sold in 2008. In 2008 Daniel Müller in a team with Carsten Werner and Ulrich Nienhaus launched a new BMBF research center for Molecular Bioengineering (B CUBE, www.bcube-dresden.de) at the TU Dresden. In December 2010 Müller accepted the Chair of Bionanotechnology at the ETH Department of Biosystems Science and Engineering (D-BSSE) in Basel. Together with Wolfgang Meier (Uni Basel) Daniel Müller in 2014 launched and co-directs the Swiss National Competence Center of Research (NCCR) Molecular Systems Engineering at Basel (www.nccr-mse.ch).
Mechanically Detecting and Directing Molecular and Cellular Processes towards Controlling Organisms
Mechanobiology emerges at the crossroads of medicine, biology, biophysics and engineering and describes how the response of proteins, cells, tissues and organs to mechanical cues contribute to development, differentiation, physiology and disease. The grand challenge in mechanobiology is to quantify how biological systems sense, transduce, respond and apply mechanical signals. Over three decades, atomic force microscopy (AFM) has emerged as a key platform enabling the simultaneous morphological and mechanical characterization of living biological systems. Here, I will introduce the use of AFM-based nanoscopic assays to characterize the mechanical process guiding the drastic shape change of animal cells progressing through mitosis. We apply our assay in a massive screen to study the contribution of > 1’000 individual human genes in mitotic cell shape change. After having found the major genes responsible for regulating cell shape changes in mitosis, we apply our assay to control cancer cells progressing through mitosis. After this, we introduce high-resolution AFM-based assays to characterize individual cellular machines (proteins) playing commanding roles in animal cells. First, we developed AFM-based imaging to observe cellular machines at sub-nanometer resolution at work. Second, we extended these imaging possibilities of AFM to image native membrane receptors and at the same time detect their interactions and binding steps to ligands and determine the free-energy landscape of the receptor-ligand bonds. Thereby the approach can distinguish between ligands representing either agonists, inverse agonists or antagonists. Third, we apply AFM-based single-molecule force spectroscopy to image and structurally map, at amino acid accuracy, the interactions that functionally modulate a membrane receptor. Fourth, we will exemplify how to use AFM-based assays to characterize viruses binding to mammalian cells and demonstrate how to use these insights to direct virus infection in vitro and in vivo for controlling cellular function and to restore vision. Finally, I will overview recent developments of force nanoscopy, which applied together with modern light microscopy and cell biological and genetic tools, provide unique fascinating insight into how the machinery of the cell contributes to basic processes of life.
 Atomic force microscopy imaging modalities in molecular and cell biology. Y.F. Dufrêne, T. Ando, R. Garcia, D. Alsteens, D. Martinez-Martin, A. Engel, C. Gerber & D.J. Müller. Nature Nanotechnology (2017) 3, 295-307.
 Atomic force microscopy-based characterization and design of biointerfaces. D. Alsteens, H.E. Gaub, R. Newton, M. Pfreundschuh, C. Gerber & D.J. Müller. Nature Review Materials (2017) 2, 17008.
 Combined activities of hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding. M.P. Stewart, J. Helenius, Y. Toyoda, S.P. Ramanathan, D.J. Muller & A.A. Hyman. Nature (2011) 469, 226-230.
 Cdk1 dependent mitotic enrichment of cortical myosin II promotes cell rounding against confinement. S.P. Ramanathan, J. Helenius, M.P. Stewart, C. Cattin A.A. Hyman & D.J. Muller. Nature Cell Biology (2015) 17, 148-159.
 Mechanical control of mitotic progression in single animal cells. C.J. Cattin, M. Düggelin, D.M. Martinez, C. Gerber, D.J. Müller & M.P. Stewart. Proc. Natl. Acad. Sci. USA (2015) 112, 11258-11263.
 Cholesterol increases kinetic, energetic and mechanical stability of the human b-adrenergic receptor. M. Zocher, C. Zhang, G.F.S. Rassmussen, B.K. Kobilka & D.J. Muller Proc. Natl. Acad. Sci. USA (2012) 109, E3463-3473.
 Five challenges to bringing single-molecule force spectroscopy into the living cell. Y.F. Dufrene, E. Evans, A. Engel, J. Helenius, H.E. Gaub & D.J. Muller Nature Methods (2011) 8, 123-127.
 Multi-parametric force mapping of biological systems to molecular resolution. Y.F. Dufrene, D. Martinez-Martin, I. Medalsy, D. Alsteens & D.J. Muller Nature Methods (2013) 10, 847-854.
 Imaging G protein-coupled receptors while quantifying their ligand-binding free-energy landscape. D. Alsteens, M. Pfreundschuh, C. Zhang, P. Spoerri, S.R. Coughlin, B.K. Kobilka & D.J. Müller Nature Methods (2015) 12, 845-851.
 Nanomechanical mapping of first binding steps of a virus to animal cells. D. Alsteens, R. Newton, R. Schubert, D. Martinez-Martin, B. Roska & D.J. Müller. Nature Nanotechnology (2017) 12, 177-183.
 Genome-scale single-cell mechanical phenotyping reveals disease-related genes involved in mitotic rounding. Y. Toyoda, C.J. Cattin, M.P. Stewart, I. Poser, M. Theis, T.V. Kurzchalia, F. Buchholz, A.A. Hyman & D.J. Müller. Nature Communications (2017) 8, 1266.
 Inertial picobalance reveals fast mass fluctuations of mammalian cells. D. Martínez-Martín, G. Fläschner, B. Gaub, S. Martin, R. Newton, C. Beerli, J. Mercer, C. Gerber & D.J. Müller. Nature (2017) 550, 500-505.
 Virus stamping for targeted single cell infection in vitro and in vivo. R. Schubert, et al. Nature Biotechnology (2018) 36, 85-88.