Welcome to the Simmel lab - Physics of Synthetic Biological Systems

Our goal is the realization of self-organizing molecular and cellular systems that are able to respond to their environment, compute, move, take action. On the long term, we envision autonomous systems that are reconfigurable, that can evolve and develop.

DNA biochips: strand displacement lithography and gene expression
Electrical control of a self-assembled nanoscale robot arm
Molecular transport through large-diameter DNA nanopores
DNA condensation along pre-designed paths
DNA origami rotaxanes
Chemical communication between bacteria and droplets

DNA biochips: strand displacement lithography and gene expression. We present a biocompatible, DNA-based resist termed "Bephore" based on commercially available components, which can be patterned by both photo- and electron beam lithography. Bephore is well suited for multi-step lithographic processes, enabling the immobilization of different types of DNA molecules with micrometer precision, as shown in the miniaturized, fluorescent DNA-based replica of Franz Marc's painting "Tiger" (1912). As an application, we demonstrate compartmentalized, on-chip gene expression from three sequentially immobilized DNA templates, leading to spatially resolved protein expression gradients.

G. Pardatscher, M. Schwarz-Schilling, S. S. Daube, R. H. Bar-Ziv, and F. C. Simmel, Gene Expression on DNA Biochips Patterned with Strand Displacement Lithography. Angewandte Chemie International Edition 57,
4783-4786 (2018). DOI: 10.1002/anie.201800281

News and Views (Nature Chemistry): Link

Electrical control of a self-assembled DNA robot arm. We have created a nanoscale platform of size 55 nm x 55 nm with an integrated molecular arm that can rotate around a hinge in the center of the platform. In contrast to previous work on molecular machines based on DNA molecules, we utilized electrical fields to  drive and control the motion of the arm with respect to the platform. With this technique, we can switch the position of the arm within milliseconds, which allows fast transport of molecules and nanoparticles. The robot arm can also be used to exert forces in the pico-Newton range, which is demonstrated in DNA unzipping experiments. Importanly, electrical manipulation allows us to realize complex, computer-controlled movement patterns.

E. Kopperger*, J. List*, S. Madhira, F. Rothfischer, D. C. Lamb, and F. C. Simmel, A self-assembled nanoscale robotic arm controlled by electric fields, Science 359, 296–301 (2018). DOI: 10.1126/science.aao4284

Molecular transport through large-diameter DNA nanopores. Artificial lipid membrane channels can be created from DNA using the origami technique. Here we demonstrate a DNA channel design consisting of a flat plate that can firmly attach to a bilayer membrane and a central stem that punches through the membrane, thus creating a pore with a diameter of about 4 nm. We show that the membrane channel conducts ionic current and can be used to electrophoretically transport double-stranded DNA across the membrane. Moreover - as indicated in the figure - the channels spontaneously insert into the membranes of giant liposomes and thus allow molecules to diffuse into and out of the vesicles.

S. Krishnan, D. Ziegler, V. Arnaut, T. G. Martin, K. Kapsner, K. Henneberg, A. R. Bausch, H. Dietz, F. C. Simmel, Molecular transport through large-diameter DNA nanopores, Nature Communications 7:12787 (2016). DOI: 10.1038/ncomms12787

DNA condensation along pre-designed paths. DNA condensation is a process known for its biological function in the regulation of genes and metabolism, and for the generation of peculiar nanostructures such as DNA toroids. In collaboration with the group of Roy H. Bar-Ziv (Weizmann Institute, Israel) we investigated the condensation of e-beam patterned, surface-bound DNA brushes into arbitrarily shaped DNA bundles of only 20 nm in width, but several tens of micrometers in length. We further utilized the stochastic nature of the condensation process to apply unconventional computation schemes to pathfinding in a maze and other DNA brush networks.

G. Pardatscher, D. Bracha, O. Vonshak, S. S. Daube, F. C. Simmel, R. H. Bar-Ziv, DNA condensation in one dimension, Nature Nanotechnology 11,1076–1081 (2016). DOI: 10.1038/nnano.2016.142

DNA origami rotaxanes. Molecularly interlocked structures are widely regarded as essential components of molecular machinery as they enable the long range movement of molecular parts with respect to each other. We now created some of the first DNA-based rotaxane structures using the DNA origami technique. The structures probably are the largest and most rigid rotaxanes created to date. They also represent examples  of multicomponent DNA origami nanodevices, in which multiple, freely movable molecular parts are interlocked with each other. We also demonstrate extended “pseudorotaxane” structures on which molecular rings can slide over a length of several hundred nanometer.

J. List, E. Falgenhauer, E. Kopperger, G. Pardatscher, F. C. Simmel, Long-Range Movement of Large Mechanically Interlocked DNA Nanostructures, Nature Communications 7:12414 (2016). DOI: 10.1038/ncomms12414

Chemical communication between bacteria and droplets. The integration of bacterial and chemical cells into larger systems is of great interest for the creation of synthetic multicellular structures. Here we demonstrated a simple form of spatial differentiation within linear chains of microemulsion droplets that are filled either with bacteria or with cell-free gene expression systems. Confinement of genetic inducers to diffuse in only one dimension enables strong coupling of neighboring droplet cells. We here also established chemical communication between cell-free systems and bacteria acting as senders and receivers, and vice versa.

M. Schwarz-Schilling, L. Aufinger, A. Mückl, F. C. Simmel, Chemical communication between bacteria and cell-free gene expression systems within linear chains of emulsion droplets, Integrative Biology 8, 564-570 (2016). DOI: 10.1039/C5IB00301F