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Stefan Diez
Molecular transport in cell biology and nanotechnology
Previous and current research
Our lab is interested in the development and the application of novel optical techniques to investigate molecular transport in cell biology and nanotechnology. Building on our experience in single molecule biophysics and in the in vitro reconstruction of subcellular mechano-systems we study cooperative effects in motor transport and cell motility. Moreover we aim to apply biomolecular motor systems in a synthetic, engineered environment for the generation and manipulation of nanostructures. Thereby, our main emphasis is on the development of methods to control the nano-transport sytems by external signals in a spatio-temporal manner. Towards this end we investigate novel biotemplate-based nanostructuring techniques and fabricate smart composite surfaces, where active enzymes are embedded in stimuli-responsive polymer layers.
The idea of using cellular machines in nanotechnology is intriguing because such machines are robust, can work in parallel, their size is in the nanometer range, they work with a high energy efficiency and their application is potentially cheap. Specifically we work on the setup of robust in vitro motility assays as well as on the spatial and temporal control over the motor activity by chemical, electrical and optical means. As one example, we have used purified kinesin motors in combination with chemically modified microtubules to transport and stretch individual lambda-phage DNA molecules across a surface. This technique, in contrast to existing ones, enables the parallel yet individual manipulation of many molecules and may offer an efficient mechanism for the generation of multidimensional, DNA-based nanocircuits.
a) Microtubule-DNA transport and manipulation system. Biotinylated microtubules are used to transport individual l-phage DNA molecules that are biotinylated at their ends and attached to the microtubule via a streptavidin linkage. Stretching of microtubules is achieved when a moving microtubule picks up the end of a DNA molecule which has already attached to the substrate at its other end.
b) Fluorescence micrograph of a moving microtubule (red) transporting (white arrows) and stretching individual DNA molecules. Scale bar 5 µm. (collaboration with TU Dresden, group of M. Mertig and W. Pompe)
Future prospects and goals
The group will continue to utilize biophysical processes based on the generation of force by motor proteins and microtubules to construct and manipulate molecular structures in the nanometer range. We aim to establish a toolbox of novel, actively operating bionanomechanical components such as transporters, stretchers, compressors, rectifiers, colliders and explorers. These components will then be used in the setup of molecular reaction systems, the nanometer structuring and exploration of surfaces . Highly-sensitive optical imaging techniques will be crucial for the successful implementation of biomolecular processes into engineered environments. Future work will therefore also involve the development of novel single molecule imaging techniques using nanostructured surfaces and microfluidics systems. Thus, the group will strongly focus on the interface between biology and nanotechnology - not only to fulfill nanotechnological tasks by biomolecular machines, but also to use the high potential of micro- and nanotechnology to answer questions in the fields of cell biology and biophysics.
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Selected publications
G. Fink, L. Haijdo, K. J. Skowronek, C. Reuther, A. A. Kasprzak, S. Diez. The mitotic kinesin-14 drives directional microtubule-microtubule sliding
Nat. Cell Biol., Vol. 11, no. 6, pp. 717-723, 2009
J. Bert Nitzsche, Felix Ruhnow, Stefan Diez (2008): Quantum-dot-assisted characterization of microtubule rotations during cargo transport
Nat Nanotechnol, Vol. 3, no. 9, pp. 552-556
Cecile Leduc, Felix Ruhnow, Jonathon Howard, Stefan Diez (2007): Detection of fractional steps in cargo movement by the collective operation of kinesin-1 motors. Proc Natl Acad Sci U S A, Vol. 104, no. 26, pp. 10847-10852
J. Kerssemakers, J. Howard, H. Hess, S. Diez (2006): The distance that kinesin holds its cargo away from the microtubule surface measured by fluorescence-interference-contrast microscopy. Proc Natl Acad Sci USA, vol. 103, no. 43, pp. 15812-7.
Leonid Ionov, Manfred Stamm, Stefan Diez (2006): Reversible switching of microtubule motility using thermoresponsive polymer surfaces
Nano Lett., Vol. 6, no. 9, pp. 1982-1987
J. Helenius, G. Brouhard, Y. Kalaidzidis, S. Diez, J. Howard (2006): The depolymerizing kinesin MCAK uses 1D-diffusion to rapidly target the ends of microtubules. Nature, vol. 441, 115-119.
S. Diez, C. Reuther, C. Dinu, R. Seidel, M. Mertig, W. Pompe, J. Howard (2003): Stretching and Transporting DNA Molecules Using Motor Proteins. Nano Letters, 3: 1251-1254.