Exzellenzstrategie

NanoBioPhysics and Medical Physics

We address questions of biological and medical relevance using physical methods. Our main tools are various species of scanning probe microscopes. Seeking to descend deeper and deeper into the nanoworld, we place the development of new instruments and methods with high-speed and low-noise characteristics at the foundation of our research. Our applications include visualizing the dynamic interactions of single biomolecules, revealing morphological and mechanical properties of living cells and tissues, exposing biomaterials on the molecular scale, and illuminating transport processes in artificial and natural membranes.

Contact
Prof. Dr. Tilman Schäffer

Institut für Angewandte Physik
Universität Tübingen
http://www.bioforce.uni-tuebingen.de 

Topics

Nanoanalytics, nanomedicine, cell mechanics, soft matter, surfaces, scanning probe microscopy, force spectroscopy, mechanics and dynamics of single molecules, living cells, and tissues.

Atomic Force Microscopy (AFM)

One of our goals is to image dynamic interactions between single biomolecules in real-time with the atomic force microscope (AFM). For example, we have visualized individual binding processes of the tumor suppressor protein p53 with DNA, thereby testing various interaction models.

A further goal is to deduce properties of cellular, sub-cellular, and molecular structures from the measurement of their mechanical material properties using force spectroscopy.

In order to better address those questions, we are continuously improving scanning probe microscopy instrumentation and methods. In particular, we are improving resolution and measurement speed by designing and building atomic force microscopes for small cantilevers. These small cantilevers have mechanical resonance frequencies in the Megahertz range.

The increased resolution that we obtain using small cantilevers goes hand-in-hand with increased requirements on the detection system of the atomic force microscope. We therefore develop detectors that sense decreasingly small signals from the cantilever.

Scanning Ion Conductance Microscopy (SICM)

Scanning ion conductance microscopy (SICM) is based on an electrolyte-filled nanopipette. The nanopipette acts as a probe for the locally resolved measurement of ion current over a sample surface submerged in an electrolyte. There is a strong dependence of the ion current on the pipette-surface distance, allowing us to record topography images of the surface without actually touching it. This is especially useful for the study of soft and fragile samples such as living cells.

We have been using SICM for the contact-free imaging of living cells and of lipid bilayers that are freely suspended over micrometer-sized pores. This allows performing long-term studies of the dynamics of membrane formation and destruction. With a new method that we developed recently, it becomes possible to measure local mechanical properties of living cells in a contact-free fashion.

Publications

J. Rheinlaender, S. Vogel, J. Seifert, M. Schächtele, O. Borst, F. Lang, M. Gawaz, T.E. Schäffer, “Imaging the elastic modulus of human platelets during thrombin-induced activation using scanning ion conductance microscopy.” Thrombosis and Haemostasis (in press, 2015) http://dx.doi.org/10.1160/TH14-05-0414.

K. Metzger, T. Schönberger, S. Vogel, O. Borst, P. Seizer, M. Schneider, T. Geisler, M. Chatterjee, H. Langer, D. Fuchs, F. Lang, J. Rheinlaender, T.E. Schäffer, M. Gawaz, “High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogression in mice.” Biomaterials 36, 80-80 (2015).

J. Seifert, C.M. Hammer, J. Rheinlaender, S. Sel, M. Scholz, F. Paulsen, T.E. Schäffer, “Distribution of Young’s modulus in porcine corneas after riboflavin/UVA-induced collagen cross-linking as measured by atomic force microscopy.” PLoS ONE 9, e88186 (2014).

S. Hinderer, J. Seifert, M. Votteler, N. Shen, J. Rheinlaender, T.E. Schäffer, K. Schenke-Layland, “Engineering of a bio-functionalized hybrid off-the-shelf heart valve.” Biomaterials 35, 2130-2139 (2014).

T.E. Schäffer, “Nanomechanics of molecules and living cells with scanning ion conductance microscopy.” Analytical Chemistry 85, 6988–6994 (2013).

J. Rheinlaender, A. Gräbner, L. Ott, A. Burkovski and T.E. Schäffer, “Contour and persistence length of Corynebacterium diphtheriae pili by atomic force microscopy.” European Biophysics Journal 41, 561-570 (2012).