16, 2005 -- Engineers at The University of Texas at
Austin have found a way to modify a plastic to anchor
molecules that promote nerve regeneration, blood vessel
growth or other biological processes.
In the study led by Dr. Christine Schmidt, the researchers
identified a piece of protein from among a billion
candidates that could perform the unusual feat of
attaching to polypyrrole, a synthetic polymer (plastic)
that conducts electricity and has shown promise in
biomedical applications. When the protein piece,
or peptide, was linked to a smaller protein piece
that human cells like to attach to, polypyrrole gained
the ability to attach to cells grown in flasks in
“It will be very useful from a biomedical standpoint
to be able to link factors to polypyrrole in the
future that stimulate nerve growth or serve other
functions,” said Schmidt, an associate professor
of biomedical engineering at the university.
Schmidt is the principal author for the study conducted
with colleague Dr. Angela Belcher at Massachusetts
Institute of Technology. It was published online
May 15 by the journal Nature Materials .
Polypyrrole is of interest for tissue engineering
and other purposes because it is a non-toxic plastic
that conducts electricity. As a result, it could
be used to extend previous experiments in Schmidt's
laboratory. The experiments involve wrapping a tiny
strip of plastic around damaged, cable-like extensions
of nerve cells called neurites to help them regenerate.
“We can apply an electric field to this synthetic
material and enhance neurite repair,” said Schmidt.
The newly gained ability to attach proteins to
polypyrrole, she said, will mean that growth-enhancing
factors could also be linked to this plastic wrapping,
further stimulating neurite regeneration.
Working with Schmidt and Belcher, the paper's lead
authors, graduate students Archit Sanghvi and Kiley
Miller identified the peptide that attaches to polypyrrole
from among the billion alternatives initially analyzed.
These unique peptides were displayed on the outer
surface of a harmless type of virus called a bacteriophage
that was purchased commercially.
To hunt for the plastic-preferring peptide, Sanghvi
and Miller added a solution containing bacteriophages
that displayed different peptides to a container
with polypyrrole stuck on its inner surface. The
bacteriophages that didn't wash away when exposed
to conditions that hinder attachment were retested
on a new polypyrrole-coated container, a process
that was repeated four more times.
The sticky peptide selected, known as T59, is a
string of 12 amino acids. To make certain that something
else on the outer surface of the bacteriophage virus
wasn't responsible for its perceived stickiness,
the researchers demonstrated that T59 by itself could
attach to immobilized polypyrrole, using synthetic
copies of it made at the university's Institute for
Cellular and Molecular Biology. In addition, they
determined that a certain amino acid, aspartic acid,
had to be a part of T59 for it to attach well to
Aspartic acid carries a negative charge, which in
T59 appeared to be drawn to the positively charged
surface of the polypyrrole the way magnets of opposite
charges cling together. Yet other peptides containing
aspartic acid didn't attach to polypyrrole, leading
the researchers to speculate that something contributed
by the other amino acids in T59 influenced its 3-dimensional
shape in a way that augmented its plastic preference.
“This aspartic acid is just one piece of the puzzle,” Sanghvi
said. “There are still more pieces to put together.”
researchers also evaluated how well T59 clings
to polypyrrole. They attached copies of the peptide
to the tip of an atomic force microscope at the
university's Center for Nano- and Molecular Science
and Technology. The tip of this specialized microscope
is normally passed across the surface of a material
to “map” its
peaks and valleys. In this case, the surface was
a layer of polypyrrole, and the resistance of the
peptide-coated tip to being passed across the surface
revealed how well T59 clung to the plastic.
“They had a moderately strong interaction, which
is useful to know,” Schmidt said, referring to
the need for a stable attachment between polypyrrole
and biological molecules that T59 would be used
to link to.
Schmidt's laboratory intends to study T59 as a linker
to other molecules in the future, possibly including
vascular endothelial growth factor, which stimulates
the growth of new blood vessels. In addition, they
will use the bacteriophage analysis approach, called
high-throughput combinatorial screening, to look
for peptide linkers for other plastics such as polyglycolic
acid under study for tissue-repair or tissue-engineering
“This is a powerful technique that can be used for
biomaterials modification,” Schmidt said, “and
it hasn't really been explored very much until
This research was funded by the Gillson Longenbaugh
Foundation and the Welch Foundation.