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In surprise finding, proteins self-assemble into nanofibers

By R&D Editors | March 1, 2012

Nanofiber1

During
an experiment that involved studying certain cylinder-shaped proteins
derived from cartilage oligomeric matrix protein (COMP, found
predominantly in human cartilage), researchers noticed that in high
concentrations, these alpha helical coiled-coil proteins spontaneously
came together and self-assembled into nanofibers. It was a surprising
outcome.

A
new method for creating nanofibers made of proteins, developed by
researchers at Polytechnic Institute of New York University (NYU-Poly),
promises to greatly improve drug delivery methods for the treatment of
cancers, heart disorders and Alzheimer’s disease, as well as aid in the
regeneration of human tissue, bone and cartilage.

In
addition, applied differently, this same development could point the
way to even tinier and more powerful microprocessors for future
generations of computers and consumer electronics devices.

The
details are spelled out in an which appears online in Advanced
Functional Materials
. Author Susheel K. Gunasekar, a doctoral student in
NYU-Poly’s Department of Chemical and Biological Sciences, was the
primary researcher, and is a student of co-author Jin Montclare,
assistant professor and head of the department’s Protein Engineering and
Molecular Design Lab, where the underlying research was primarily
conducted. Also involved were co-authors Luona Anjia, a graduate
student, and Professor Hiroshi Matsui, both of the Department of
Chemistry and Biochemistry at Hunter College (The City University of New
York), where secondary research was conducted.

Yet
all of this almost never emerged, says Professor Montclare, who
explains that it was sheer “serendipity”—a chance observation made by
Gunasekar two years ago—that inspired the team’s research and led to
its significant findings.

During
an experiment that involved studying certain cylinder-shaped proteins
derived from cartilage oligomeric matrix protein (COMP, found
predominantly in human cartilage), Gunasekar noticed that in high
concentrations, these alpha helical coiled-coil proteins spontaneously
came together and self-assembled into nanofibers. It was a surprising
outcome, Montclare says, because COMP was not known to form fibers at
all.

“We
were really excited,” she recalls. “So we decided to do a series of
experiments to see if we could control the fiber formation, and also
control its binding to small molecules, which would be housed within the
protein’s cylinder.”

Of
special interest were molecules of curcumin, an ingredient in dietary
supplements used to combat Alzheimer’s disease, cancers and heart
disorders.

By
adding a set of metal-recognizing amino acids to the coiled-coil
protein, the NYU-Poly team succeeded, finding that the nanofibers alter
their shapes upon addition of metals such as zinc and nickel to the
protein. Moreover, the addition of zinc fortified the nanofibers,
enabling them to hold more curcumin, while the addition of nickel
transformed the fibers into clumped mats, triggering the release of the
drug molecule.

Next,
Montclare says, the researchers plan to experiment with creating
scaffolds of nanofibers that can be used to induce the regeneration of
bone and cartilage (via embedded vitamin D) or human stem cells (via
embedded vitamin A).

Later,
it may even be possible to apply this organic, protein-based method for
creating nanofibers to the world of computers and consumer electronics,
Montclare says—producing nanoscale gold threads for use as circuits in
computer chips by first creating the nanofibers and then guiding that
metal to them.

Ultimately,
Montclare says, the researchers would like the fruits of their
discovery—such therapeutic nanofibers and metallic nanowires—to be
adopted by pharmaceutical companies and microprocessor makers alike.

Funding
for this NYU-Poly research was provided by the U.S. Air Force Office of
Scientific Research, the U.S. Army Research Office, the U.S. Department
of Energy and the National Science Foundation.

Effects of Divalent Metals on Nanoscopic Fiber Formation and Small Molecule Recognition of Helical Proteins

SOURCE

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