Johns Hopkins researchers have created a new class of
artificial proteins that can assemble themselves into a gel
and encourage the growth of selected cell types. This
biomaterial, which can be tailored to send different
biological signals to cells, is expected to help scientists
who are developing new ways to repair injured or diseased
"We're trying to give an important new tool to tissue
engineers to help them do their work more quickly and
James L. Harden, whose lab team developed the new
biomaterial. "We're the first to produce a self-assembling
protein gel that can present several different biological
signals to stimulate the growth of cells."
Harden, an assistant professor in the Whiting School's
Department of Chemical
and Biomolecular Engineering, reported on his work
March 28 in Anaheim, Calif., at the 227th national meeting
of the American Chemical Society.
Tissue engineers use hydrogels, which are
macromolecular networks immersed in an aqueous environment,
to provide a framework or scaffold upon which to grow
cells. These scientists hope to advance their techniques to
the point where they can treat medical ailments by growing
replacement cartilage, bones, organs and other tissue in
the lab or within a human body.
The Harden lab's new hydrogel is made by mixing
specially designed modular proteins in a buffered water
solution. Each protein consists of a flexible central coil
containing a bioactive sequence and flanked by helical
associating modules on each end. These end-modules come in
three distinct types, which are designed to attract each
other and form three-member bundles. This bundling leads to
the formation of a regular network structure of proteins
with three-member junctions linked together by the flexible
coil modules. In this way, the new biomaterial assembles
itself spontaneously when the protein elements are added to
The assembly process involves three different "sticky"
ends. But between any two ends, Harden can insert one or
more bioactive sequences, drawing from a large collection
of known sequences. Once the gel has formed, each central
bioactive module is capable of presenting a specific
biological signal to the tissue engineer's target cells.
Certain signals are needed to encourage the adhesion,
proliferation and differentiation of cells in order to form
particular types of tissue.
Harden's goal is to provide a large combinatorial
"library" of these genetically engineered proteins. A
tissue engineer could then draw from this collection to
create a hydrogel for a particular purpose. "We want to let
the end-user mix and match the modules to produce different
types of hydrogels for selected cell and tissue engineering
projects," he said.
Harden believes this technique may speed up progress
in the tissue engineering field. For one thing, tissue
engineers would not have to do complex chemistry work to
prepare a hydrogel for each specific application; his
hydrogels form spontaneously upon mixing with water. Also,
unlike hydrogels that are made from synthetic polymers, the
Harden team's hydrogels are made of amino acids, the native
building blocks of all proteins within the body. Finally,
more than one protein signaling segment can be included in
the Harden team's hydrogel mix, allowing a tissue engineer
to send multiple signals to the target cells, thereby
supporting the simultaneous growth of several types of
cells within one tissue.
"Our philosophy is to take a minimalist approach,"
Harden said. "Our hydrogels are designed to send only the
growth signals that are needed for a particular
Harden's colleagues in the hydrogel research are Lixin
Mi, who earned his doctorate at Johns Hopkins and now is a
postdoctoral researcher at the National Institutes of
Health; and Stephen Fischer, a current doctoral student in
the Department of Chemical and Biomolecular Engineering.
The Harden team's research was supported by a grant
from NASA through the Program on Human Exploration and
Development of Space. Stephen Fischer is also supported by
a NASA Graduate Student Researchers Program fellowship.