„Dynamics and Signalling of Hsp90 by multi-color FRET and optical tweezers”

Molecular Machines

We have developed a multi-color single molecule FRET setup with alternating laser excitation combined with microfluidics to observe the mechano-chemistry of the heat shock protein and molecular chaperone Hsp90. Our data has demonstrated a scissor-like opening and closing of Hsp90 and resolved many details of the mechanism of the energy conversion in this fascinating molecular machine. Such molecular details are not only important to understand the fundamentals of biological molecular machines, but also for medical purposes (e.g. a controlled inhibition of Hsp90 might stop the division of cancer cells).

Our setup has just been extended towards four colour FRET and a combination of single molecule fluorescence and Magnetic Tweezers. This allows us to investigate more complex biological systems, like Hsp90 interaction with its cochaperones, substrate proteins or drugs. The focus will be on cooperativity and coordination in these interactions as well as on in vitro structure. 

 

 

„Nanoscopic fundamentals of Friction and Adhesion in thin films and cartilage“

Polymers at Interfaces

Polymer-solid contacts play an important role in biotechnology, from the adhesion of coatings (which are present in most modern materials) to nano-composites. Yet, a fundamental understanding of their interface – especially in aqueous environment - is still missing. We probe single polymer adhesion and friction near solid substrates in order to find the parameters which most effectively control the polymer-solid interface, both with AFM and single molecule tracking. This knowledge will also be essential for the development of glues and lubricants, which we investigate in collaboration with the BMW AG. In addition, we use our AFM-based methods to understand friction and lubrication in cartilage.

We also study the physical principles underlying the hydrophobic interaction and compare the results with MD-Simulations. We made several surprising observations: i) At interfaces in aqueous environment dispersion forces and water structure forces largely compensate, similar to entropic and enthalpic contributions in the protein folding problem. ii) The adhesion on the nano-scale cannot simply be scaled to the macroscopic scale. Therefore, our future aim is to figure out how the properties of nanoscopic units make up macroscopic objects to guide the design of functional surface coatings.