Welcome to the Liedl Research Group on Molecular Self-Assembly and Nanoengineering!
We are interested in molecular self-assembly processes in general and particularly in the engineering of functional DNA devices using the DNA origami method. We will focus on the integration of self-assembled DNA nanostructures with lithographically defined environments. We hope to combine well-established lithography methods with the advantages of self-assembly and molecular addressability.
The design of functional DNA hybrid materials and its characterization will also help us to understand the mechanical and chemical interactions across multiple levels of organization between the different molecular components in living cells and tissues.
DNA Origami
The achievable complexity of man-made DNA structures has taken a great leap forward with the recent invention of 2D DNA origami by Paul Rothemund (Rothemund, P. W. K., Nature, 2006). This technique employs a virus-based DNA single strand (7 kb long) as a scaffold which is brought into shape by hundreds of short oligonucleotides. In 2009 we have shown in the group of William Shih that this method can be extended to three dimensions and that arbitrary nanoscale shapes can be realized (Douglas, S. M. et al., Nature, 2009). These three-dimensional (3D) DNA origami structures can multimerize into rigid objects spanning micrometers in length while they are addressable with nanometer precision.
The fine positional accuracy offered by 3D DNA origami nanostructures will help us bridge the gap between the macroscopic and the nanoscopic world and will enable us to investigate biomolecular (model) systems at unprecedented levels of control. Please find below a few of the research topics pursued in our lab.
- S. M. Douglas, H. Dietz, T. Liedl, B. Högberg, F. Graf, and W. M. Shih, Self-assembly of DNA into nanoscale three-dimensional shapes, Nature 459, 414–418 (2009)
Current Research Interests
Tensegrity and Mechano-transduction
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Tensegrity - a fusion of the words tension and integrity - is a building principle that is based on the balanced distribution of continuos tension over a structure composed from compression-resistant elements connected by tension bearing components ( http://en.wikipedia.org/wiki/Tensegrity, http://www.kennethsnelson.net/ ). Such tensed networks exhibit remarkable features such as high overall stability and the potential of reorganization and self-stabilization during and after external distortions while relatively small amounts of material are needed for their assembly. On the cellular level, the tensegrity model suggests that mechanical stresses acting on surface receptors that physically couple the cytoskeleton to the extracellular matrix can be translated into a sudden behavioral response of the cell since a local distortion can be propagated immediately over a whole tensed structure ( http://www.childrenshospital.org/research/ingber/Tensegrity.html ).
We have succeeded in building such prestressed three-dimensional tensegrity structures from DNA. For this endeavor we build compression resistant struts using the DNA origami method and connected the ends of the struts with long unpaired regions of ssDNA that act as entropic springs. This way we are able to create networks of controllable geometry and tension.
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Functionalization of DNA origami structures
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Using the DNA origami approach we are now able to manufacture nanoscale objects of desired shapes which potentially offer a wide range of (bio-)chemical groups with defined position and orientation in space. We can exploit this technique to specifically functionalize DNA nanostructures with metal nanoparticles and organic or inorganic fluorophores. The assembly of partly metallized DNA structures which exhibit fluorophores at designated positions will be pursued in order to gain insight in energy transfer and energy funneling processes.
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Chemical Gradients over time and space
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We demonstrated a novel approach to determine the melting temperature of DNA duplexes in a fast and efficient way using stable gradients of a denaturing agent generated in a multilayer microfluidic setup. This offers the usual advantages of miniaturized analytical systems such as low sample consumption, speed (in this case a several hundredfold speed-up compared to conventional melting point determination), scalability and the potential of integration with other analysis system. In addition, the method is as accurate as conventional methods and is shown to be sensitive to a single nucleotide mismatch which is of interest in the context of SNP detection.
DNA origami structures can self-assemble at room temperature (in contrast to temperature ramps, which are usually used to facilitate the self-assembly process of DNA nanostructures) when exposed to slowly decreasing concentrations of denaturing agents. This assembly method will allow for the integration of temperature-sensitive components into DNA nanostructures.
- T. Liedl and F. C. Simmel, Determination of DNA melting temperatures in diffusion-generated chemical gradients, Analytical Chemistry 79, 5212-5216 (2007)
- R. Jungmann, T. Liedl, T. L. Sobey, W. M. Shih, and F. C. Simmel, Isothermal assembly of DNA origami structures using denaturing agents, J. Am. Chem. Soc. 130, 10062-10063 (2008)
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DNA-crosslinked Hydrogels
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Using double-stranded DNA as a reversible crosslinker for polyacrylamide provides the possibility to generate biocompatible and sequence programmable gels. The pore size and mechanical properties of such gels is adjustable by choosing the appropriate length of the DNA crosslinker strands. The diffusion properties of fluorescent semiconductor nanoparticles in such DNA-switchable hydrogels can be studied using single-quantum-dot tracking and fluorescence correlation spectroscopy.
We want to investigate the behavior of nanoparticle loaded microgels in cell cultures. Here, the release of the particles could be triggered by naturally occurring RNA molecules.
- T. Liedl, H. Dietz, B. Yurke, and F. C. Simmel, Controlled trapping and release of quantum dots in a DNA-linked hydrogel, Small 3, 1688-1690 (2007)
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Labs and researchers in the field (not a complete list):
Hendrik Dietz (cache) @ TU München
Shawn Douglas @ Wyss Institute, Harvard University
Deborah Fygenson @ University of California Santa Barbara
Chengde Mao @ Purdue University
Niles Pierce @ Caltech
Paul Rothemund (cache) @ Caltech
Ned Seeman @ New York University
William Shih (cache) @ Harvard Medical School
Fritz Simmel @ TU München
Andrew Turberfield @ Oxford University
Erik Winfree (cache) @ Caltech
Hao Yan @ Arzona State University
Bernard Yurke @ Boise State University
Current Group Members
Wiki