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.

Communication in synthetic multicellular systems
Autonomously growing peptide vesicles
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

Communicating artificial cells: Multicellularity in living organisms allows for complex behavior through differentiation of cell types. We have assembled artificial cells into synthetic "microtissues” through the use of water-in-oil droplets forming lipid bilayers upon contact with each other. We established and characterized cell-to-cell communication in these artificial multicellular structures. Using different types of synthetic in vitro gene circuits, we then implemented two examples of more complex dynamical behavior in such systems: spatial propagation of a chemical signal and a simple form of cellular differentiation.

A. Dupin, F. C. Simmel, Signalling and differentiation in emulsion-based multi-compartmentalized in vitro gene circuits. Nat Chem. 11, 32–39 (2019). https://www.nature.com/articles/s41557-018-0174-9

News and Views article by Li & Schulman: https://doi.org/10.1038/s41557-018-0192-7

Artificial gel based organelles: Our artificial organelles consist of agarose hydrogel beads functionalized with DNA molecules, which either act as genetic templates or which are able to capture diffusing RNA molecules. In order to mimic artificial cells, we encapsulated the organelles within emulsion droplets containing a cell-free gene expression system. One type of organelle was used to generate mRNA molecules coding for a fluorescent protein, whose translation was inhibited in the absence of certain trigger DNA molecules. Only when the RNA diffused into organelles containing the trigger, translation of the protein was activated. In this way, similar as in eukaryotic cells, we separated genetic transcription and translation processes into distinct subcellular compartments.

L. Aufinger, F. C. Simmel, Artificial Gel-based Organelles for Spatial Organization of Cell-free Gene Expression Reactions, Angew. Chem. Int. Ed. 57, 17245-17248 (2018). DOI: 10.1002/anie.201809374

Rise of the synthetic peptide cell: Compartmentalization and growth are central aspects of living cells, but the creation of natural membrane building blocks is difficult to implement in vitro. We now created peptide-based reaction compartments which are able to grow when the membrane peptide is expressed inside of them. By encapsulating a bacterial cell extract and DNA templates for protein expression we demonstrated the production of fluorescent proteins and amphiphilic elastin-like polypeptides in vesiculo which serve as the membrane building block.

K. Vogele, T. Frank, L. Gasser, M.A. Goetzfried, M. Hackl, S.A. Sieber, F.C. Simmel, T. Pirzer, Towards synthetic cells using peptide-based reaction compartments, Nature Communications 9: 3862 (2018). DOI: 10.1038/s41467-018-06379-8

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. Angew. Chem. Int. Ed. 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