Enhanced image of a polymersome changing color under stress. |
It is helpful—even
life-saving—to have a warning sign before a structural system fails, but, when
the system is only a few nanometers in size, having a sign that’s easy to read
is a challenge. Now, thanks to a clever bit of molecular design by University of Pennsylvania
and Duke University bioengineers and chemists,
such warning can come in the form of a simple color change.
The study was conducted
by professor Daniel Hammer and graduate students Neha Kamat and Laurel Moses of
the Department of Bioengineering in Penn’s School of Engineering
and Applied Science. They collaborated with associate professor Ivan Dmochowski
and graduate student Zhengzheng Liao of the Department of Chemistry in Penn’s School of Arts and Sciences, as well as professor
Michael Therien and graduate student Jeff Rawson of Duke.
Their work was published
in Proceedings of the National Academy of
Sciences.
The researchers’ work
involves two molecules: porphyrins, a class of naturally occurring pigments,
and polymersomes, artificially engineered capsules that can carry a molecular
payload in their hollow interiors. In this case, Kamat and Liao hypothesized
that polymersomes could be used as stress sensors if their membranes were
embedded with a certain type of light-emitting porphyrins.
The Penn researchers
collaborated with the Therien lab, where the porphyrins were originally developed,
to design polymersomes that were studded with the light-emitting molecules.
When light is shined on these labeled polymersomes, the porphyrins absorb the
light and then release it at a specific wavelength, or color. The Therien lab’s
porphyrins play a critical role in using the polymersomes as stress sensors,
because their configuration and concentration controls the release of light.
“When you package these
porphyrins in a confined environment, such as a polymersome membrane, you can
modulate the light emission from the molecules,” Hammer says. “If you put a
stress on the confined environment, you change the porphyrin’s configuration, and,
because their optical release is tied to their configuration, you can use the
optical release as a direct measure of the stress in the environment.”
For example, the labeled
polymersomes could be injected into the blood stream and serve as a proxy for
neighboring red blood cells. As both the cells and polymersomes travel through
an arterial blockage, for example, scientists would be able to better
understand what happens to the blood cell membranes by making inferences from the
stress label measurements.
The researchers
calibrated the polymersomes by subjecting them to several kinds of controlled
stresses—tension and heat, among others—and measuring their color changes. The
changes are gradations of the near infrared spectrum, so measurements must be
made by computers, rather than the naked eye. Rapidly advancing body-scanning
technology, which uses light rather than magnetism or radiation, is well suited
to this approach.
Other advances in medicine
could benefit, as well. As cutting-edge pharmaceutical approaches already use
similar molecular technology, the researchers’ porphyrin labeling system could
be integrated into medicine-carrying polymersomes.
“These kinds of tools
could be used to monitor drug delivery, for example,” Kamat says. “If we have a
way to see how stressed the container is over time, we know how much of the
drug has come out.”
And, though the
researchers chose the engineered polymersomes due to the wide range of stress
they can endure, the same stress-labeling technique could soon be applied
directly to naturally occurring tissues.
“One future application
for this is to use dyes like these porphyrins but include them directly in a
cellular membranes,” Kamat says. “No one has taken a look at the intrinsic
stress inside a membrane so these molecules would be perfect for the job.”
Filed Under: Drug Discovery
