Thursday, 17 March 2016 16:03

MOSAIC: New platform for signal transduction analyses in cells Featured

Scientists from the Institute for Biological Interfaces at Karlsruhe Institute of Technology (KIT), headed by Prof. Christoph Niemeyer have developed a platform that can be used to study fundamental aspects of early stages of signal transduction in living cells.

The platform is called MOSAIC (Multiscale Origami Structures As Interface for Cells). Origami is actually called "paper folds". This research has also to do with folding, DNA folding. The researchers have constructed pegboards for long DNA fragments that fold themselves organized according to a precise plan in 100 nanometers and 50 nanometers wide plates. The pegboards are able to bind signaling molecules at specific locations. The scientists have placed signaling molecules at a distance of 5 nanometers on the tiny pegboards. then, the researchers have printed matching DNA foundations on cellular carriers (microarrays), which they were able to bind. In this way they succeeded in attaching a variety of pegboards on a microarray.
In a proof-of-principle study, the researchers tested the functionality of its platform by investigantion of a common breast cancer cell line (MCF-7) as cell model on their responsiveness to ligands (signaling molecules of the system). For this, the patch panels were constructed with EGF molecules (ligands for the so-called epithelial growth factor (EGFR))and thereafter CF-7 cells applied. By binding (phosphorylation) activated receptors of the individual MCF-7 cells were visualized by antibody staining.

With high accuracy, with the MOSAIC method molecules of measuring 50 by 100 nanometers size can be positioned on a pegboard.
(Photo: KIT)

In this proof-of-principle study it was shown quantitatively that in populated pegboards on the cell carrier of different density the cells also reacted with varying intensity. Of course on the slots various ligands can be applied. In the next step, the researchers want to investigate whether they can address multiple receptors of cells with multiple ligands, whether this is done in combination one by one and what distance the ligand is nessessary to be recognized by the receptor. Even cellular responses downstream can be combined, if, for example cells are genetically tagged with a fluorescent protein, which e.g. always is produced and visible when in the cell a trancription factorhas been activated by one or several receptors.

Thus diseases could get examined, which e.g. are traced to a malfunction of cell receptors or signaling pathways.

Original publication:
Alessandro Angelin, Simone Weigel, Ruben Garrecht, Rebecca Meyer, Jens Bauer, Ravi Kapoor Kumar, Michael Hirtz & Christof M. Niemeyer (2015): Multiscale Origami Structures As Interface for Cells. Angew. Chem. Int. Ed. 54, 15813-15817. DOI: 10.1002 / anie.201509772