Biotechnology / Life Sciences in Baden-Wrttemberg Cell anchors - hybrid peptide-p...

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Cell anchors - hybrid peptide-polymer molecules

Nature is an excellent source of inspiration for scientists. Dr. Markus Biesalski, a
chemist from Freiburg, uses small protein components (peptides) to coat surfaces of
solid bodies. These peptides are joined with polymer molecules to form peptidepolymer hybrids. Surfaces that are coated with such peptide-polymer constructs are
able to determine the localisation (adhesion) and structure of cells.
The chemist, who is currently working on his habilitation at the Institute of Microsystem
Technology (IMTEK) in Freiburg, is working to connect peptides with polymers and hoping to be
able to develop functional and structurally defined materials that can be used for the production
of bioactive surfaces. The aim of his project is to attach cells at specific points on a modified
surface in order to develop innovative biochips. Biochips are similar to computer chips small
silicon, glass or plastic slides on which, instead of electric wires and circuits, biological materials
in this case living cells are specifically anchored. Such cell chips can later be used for drug
and toxicity testing or the generation of more complex cell combinations using specific culture
methods. Biesalski is part of a DFG-funded Emmy-Noether young scientists group in Professor
Jrgen Rhes Department, which focuses on made-to-measure and microstructuring of surfaces
using thin polymer films. In cooperation with Rhe, Biesalski is also working on microstructured
surfaces that enable the cultivation of living cells in a laterally controlled manner.

There is more than glue between the cells

Nearly all types of tissue in the body are bound by the extracellular matrix, which fills the
intracellular space between the individual cells. Up until a few years ago, researchers used to
regard this matrix as a kind of glue. Nowadays, it is known that the interaction of cells and
extracellular matrix governs gene expression. This means that the binding, migration and
maturation of cells, the generation, degradation and reorganisation of tissue are controlled by
specific interactions of the cells with the extracellular matrix.
A major aspect of Biesalskis approach is that the extracellular matrix also keeps the cells in
place in order to enable their integration into larger cell assemblies. The extracellular matrix
consists of proteins such as fibronectin that are equipped with what are known as ligands to
which the cells attach by way of adhesion receptors such as integrin. This transmembrane
receptor protrudes from the cell into the extracellular matrix and into the interior of the cell.
When the cell binds to fibronectin via integrin, this connection safely anchors the cell in its
environment, and at the same time leads to a complex signalling cascade in the cells interior
which mediates cell spreading at the interface. The cell spreading is caused by the formation of
actin fibres which form the cytoskeleton of the cell.

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Fluorescence microscope image of microvascular endothelial cells on a glass substrate coated with
a peptide-polymer monolayer. The actin fibres (green) are labelled with NBD phalloidin. (Photo:
Biesalski)

Reduction to what is the most essential: the bioactive peptide sequence

The Freiburg chemist uses this binding mechanism to specifically anchor the cells to the surface
of solid bodies. Just like in the living organism, connective tissue or endothelial cells bind to the
peptide-polymer conjugates by way of their integrin receptors which, in turn, present a partial
fibronectin sequence on their surface. Biesalski reduces the big fibronectin molecule to a small
bioactive peptide sequence and binds this to synthetic polymers that can be easily immobilised
on surfaces: This is a very simple approach but still effective in imitating the extracellular
matrix. The often highly complex structure of proteins such as fibronectin makes it difficult to
use proteins as surface coating and control their interaction with the surfaces to which the
proteins are attached. In contrast, it is a lot easier to immobilise our hybrid molecules on all
kinds of different surfaces, explains Biesalski.
The chemist benefits from the fact that only a very small part of the molecule is necessary for
coupling to the integrin molecule. The cell receptor binds to a very short, highly specific
sequence that consists of three amino acids. This sequence is known as RGD ligand. We embed
this molecule in a polymer and apply this mixture in a monolayer to a planar substrate, said the
chemist referring to the fact that he and his team are able to accurately determine the amount
of peptide that they need to coat the surface.

Application in pharmacy and biomedicine

In their experiments assessing the binding behaviour the chemists add a protein-free culture
medium with cells to the coated chip. The interaction between integrin and peptide ligand must
not be disturbed by other substances. The cells then have one hour to dock to the chip, the
solution containing the unbound substances is washed off and the cells on the chip are incubated
with specific nutrients. The researchers are well aware of how many peptides they can
immobilise and the required distance of the peptides from each other on the chip surface in
order to create an optimal binding.

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Schematic representation of the generation of peptide-polymer hybrids and microstructured

peptide-polymer films on planar substrates used for the specific adhesion of living cells. (Photo:
Biesalski)

The team is also able to produce simple microarrays. We have also worked on the production of
small, stable polymer particles which carry the bioactive peptide ligands on their surface. We can
spot these particles on suitable carriers in order to produce cell microarrays, said Biesalski.
Even if their work on the peptide-polymer conjugates and their use in the biocompatibilisation of
surfaces and the generation of cell microarrays is still at the basic research stage, Biesalski is
convinced that these materials will at some point come to be used for pharmaceutical and
biomedical applications. I can envisage using these living microsystems in the field of
biocompatibilisation of implants and as innovative biosensors, for example for use in drug
screening, said Biesalski.
kb - 6 February 2007

Further information:
Dr. Markus Biesalski
Institute of Microscystem Technology
Univesity of Freiburg
Georges-Khler-Allee
79110 Freiburg
Phone: +49 (0)761/203-7160
Fax: +49 (0)761/203-7162
(1)
E-mail: biesalski@imtek.de

12.03.2007

Links on this side

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mailto:biesalski@imtek.de
http:://www.bio-pro.de/umwelt/bioenergie/index.html?lang=en
http:://www.bio-pro.de/biopolymere/index.html?lang=en
http:://www.bio-pro.de/biopolymere/clusterinformation/index.html?
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5. http:://www.biopro.de/biopolymere/firmenportraets_biopolymere/index.html?lang=en
6. http:://www.biopro.de/biopolymere/clusterinformation/projekte/index.html?lang=en
7. http:://www.bio-pro.de/biopolymere/artikelliste_biopolymere/index.html?
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8. http:://www.bio-pro.de/biopolymere/kontakt_anfahrt/index.html?
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9. http:://www.bio-pro.de/umwelt/aktuelles/index.html?lang=en
10. http:://www.bio-pro.de/umwelt/um/index.html?lang=en
11. http:://www.bio-pro.de/umwelt/links/index.html?lang=en
12. http:://www.bio-pro.de/umwelt/kooperationspartner/index.html?lang=en
13. http:://www.bio-pro.de/umwelt/kontakt/index.html?lang=en
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