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Dr. Regine Kleber and

María García

infoCmt9∂heika-research de

Multi-scale DNA structures for synthetic biology of cell-matrix interactions

Multi-scale DNA structures for synthetic biology of cell-matrix interactions
Contact:

Priv. Doz. Dr. Dr. Elisabetta Cavalcanti-Adam, Institute of Physical Chemistry, University of Heidelberg.

Prof. Dr. Christof Niemeyer, Institute for Biological Interfaces-1, KIT.

Project Group:

Synthetic Biology

Startdate:

01.01.2017

Enddate:

31.12.2017

We propose a synthetic biology approach, which combines the investigative nature of biology with the constructive nature of engineering, to establish a novel toolbox for exploration and exploitation of cell-extracellular matrix (ECM) adhesion, crucial for development and function of multicellular organisms. Integrins are transmembrane receptors that bind to ECM proteins; following integrin clustering, several intracellular proteins are recruited to establish anchorage to the actin cytoskeleton and formation of focal adhesions (FAs). It is not known how many ECM binding sites are locally presented to a single cell and to which extent their nanoscale arrangement allows integrin clustering and FAs assembly. The Cavalcanti lab (Uni HD) investigates how the binding and clustering of different integrin subtypes regulates cell adhesion and migration using integrin ligands immobilized on nanopatterned surfaces.
However, this technology does neither allow for controlling the number of ligands nor for presenting multi-feature ligand arrays to single receptor binding sites. The Niemeyer lab (KIT) has recently developed the novel MOSAIC technology wherein top-down patterning of surfaces is combined with bottom-up self-assembly of DNA nanostructures to present precisely defined nanoscale patterns of ligands to cells. This project aims to harness MOSAIC for integrin ligand display to investigate and control cell adhesion. Specifically, we will generate surfacebound Molecular architectures containing varying numbers of ligands with variable affinities for integrins to investigate their effects on temporal assembly of integrin clusters and recruitment of FA proteins in living cells. We envision to exploit the detailed understanding of cell-ECM adhesion to selectively trigger intracellular programs, e.g., switch cells between adhesion and migration by nanoscale assemblies which regulate FAs assembly and dynamics, to open up novel avenues for tissue engineering.