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From Genes to Protein Mechanics on a Chip

Munich, November 17, 2014

Mechanical forces play a pivotal role in biological systems by performing tasks such as guiding cell adhesion, inducing gene expression patterns and directing stem cell differentiation. At the molecular level, mechano-sensitive proteins act as sensors and transducers, communicating the presence and direction of applied forces to downstream signaling cascades. With the rapid development of single molecule techniques, the underlying chanisms have now become accessible.

fig2chip_web_m Conformational changes in response to mechanical forces and energetic barriers along unfolding pathways can be probed by single-molecule force spectroscopy (SMFS) techniques. Prof. Hermann Gaub and colleagues from the Chair for Applied Physics and Biophysics at the Physics Department of the LMU developed a micro-fluidics platform for on-chip expression, covalent surface attachment and measurement of single-molecule protein mechanical properties. As "handles" they employed molecular components of the cellulosome, an extracellular organelle from anaerobic lignocellulose-degrading bacteria.

fig3fibronectin_web_mThese stable molecular handles allowed them to perform thousands of mechanical experiments with each protein, using a single cohesin-modified cantilever. The ability to synthesize and probe protein libraries enables high-throughput mechanical phenotyping. With an investigation of a spectrum of different proteins with different mechanical functions originating from the intra and extracellular domains, the authors of the article which was published in the Nov. 14 issue of Nature Methods could show that their approach provides a detailed insight into the mechano-biology of proteins and promises valuable answers to a broad range of interesting questions.

This work was supported by the ERC Advanced Grant "CelluFuel", a Branco Weiss Fellowship from the ETH Zürich, the Deutsche Forschungsgemeinschaft ((SFB 1032), the Clusters of Excellence “Center for Integrated Protein Science Munich (CIPSM)” and “Nanoscience Initiative Munich” (NIM)).

Marcus Otten, Wolfgang Ott, Markus A Jobst, Lukas F Milles, Tobias Verdorfer, Diana A Pippig, Michael A Nash & Hermann E Gaub
Nature Methods 11(11): 1127-1130, 2014