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Cellular Imaging and Nanoanalytics

We combine microfluidics and electron microscope to study cellular structures and mechanisms.

The exact architecture of proteins and cellular arrangements is vital for cells and organisms. The study of these structures is essential to understand the underlying biological mechanisms. Electron microscopy radically changed how we do that. Thereby, sample preparation is a critical success factor. Miniaturized systems enable the structural characterization of cellular components not accessible before and allow new ways to study the single-cell proteome.

Microfluidics to solve sensitive protein structures
Cryo-electron microscopy (cryo-EM) only needs several thousand to a few million imaged particles to calculate a high-resolution structure and build an atomic model. Unfortunately, classical methods are a bottleneck since they employ lengthy and harsh procedures requiring large protein amounts.

We address these limitations by combining electron microscopy and microfluidics. This allows cryo-EM specimen preparation from nanoliter-sized samples in a gentle and lossless manner. Notably, microfluidics also allows the isolation and purification of proteins from a tiny amount of starting material. We foresee this new method to characterize proteins, which did not withstand the harsh isolation procedure, or could not be produced in the needed amounts before.

Single-cell proteomics to study neurodegenerative diseases
We combine a single-cell picker with the microfluidic sample preparation method to prepare an individual cell’s proteome for imaging by electron microscopy. The proteins are analyzed according to their shape. As an example, this allows detecting proteome-wide structural changes between a healthy and a diseased cell. We employ this method to study the cell to cell progression-mechanism involved in Parkinson’s disease. 

Team

Research Associates

Postdoctoral Fellows

Master Students

Publications

2019

Oliva, Paolo; Bircher, Benjamin Andreas; Schoenenberger, Cora-Ann; Braun, Thomas (2019). Array based real-time measurement of fluid viscosities and mass-densities to monitor biological filament formation. Lab on a chip, 19 (7), 1305-1314.

2017

Arnold, Stefan A.; Albiez, Stefan; Bieri, Andrej; Syntychaki, Anastasia; Adaixo, Ricardo; McLeod, Robert A.; Goldie, Kenneth N.; Stahlberg, Henning; Braun, Thomas (2017). Blotting-free and lossless cryo-electron microscopy grid preparation from nanoliter-sized protein samples and single-cell extracts. Journal of Structural Biology, 197 (3), 220-226.

2016

Arnold, Stefan A.; Albiez, Stefan; Opara, Nadia; Chami, Mohamed; Schmidli, Claudio; Bieri, Andrej; Padeste, Celestino; Stahlberg, Henning; Braun, Thomas (2016). Total Sample Conditioning and Preparation of Nanoliter Volumes for Electron Microscopy. ACS Nano, 10 (5), 4981-8.

Bircher, Benjamin A.; Krenger, Roger; Braun, Thomas (2016). Automated high-throughput viscosity and density sensor using nanomechanical resonators. Sensors and Actuators B: Chemical, 223, 784-790.

2014

Bircher, Benjamin A.; Krenger, Roger; Braun, Thomas (2014). Influence of squeeze-film damping on higher-mode microcantilever vibrations in liquid. EPJ Techniques and Instrumentation, 1, 10.

2013

Bircher, Benjamin A.; Dümpelmann, Luc; Renggli, Kasper; Lang, Hans Peter; Gerber, Christoph; Bruns, Nico; Braun, Thomas (2013). Real-Time Viscosity and Mass Density Sensors Requiring Microliter Sample Volume Based on Nanomechanical Resonators. Analytical Chemistry, 85 (18), 8676-83.

2010

Backmann, Natalija; Kappeler, Natascha; Braun, Thomas; Huber, François; Lang, Hans-Peter; Gerber, Christoph; Lim, Roderick Y. H. (2010). Sensing surface PEGylation with microcantilevers. Beilstein Journal of Nanotechnology, 1, 3-13.

2000

Braun, Thomas; McIlhinney, R. A. Jeffrey; Vergères, Guy (2000). Myristoylation-dependent N-terminal cleavage of the myristoylated alanine-rich C kinase substrate (MARCKS) by cellular extracts. Biochimie, 82 (8), 705-15.

Braun, Thomas; Philippsen, Ansgar; Wirtz, Sabine; Borgnia, Mario J.; Agre, Peter; Kühlbrandt, Werner; Engel, Andreas; Stahlberg, Henning (2000). The 3.7 projection map of the glycerol facilitator GlpF: A variant of the aquaporin tetramer. EMBO Reports, 1 (2), 183-189.

Braun, T.; Philippsen, A.; Wirtz, S.; Borgnia, M.; Agre, P.; Kühlbrandt, W.; Engel, A.; Stahlberg, H.: GlpF : a structural variant of the aquaporin tetramerMolecular biology and physiology of water and solute transport, New York: Kluwer Academic, 13-22.


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