A net with large holes won't catch small fish.
Likewise, the microscopic fibers in the protective
mucus coatings of the eyes, lungs, stomach or reproductive
system naturally bundle together and allow
the tiniest disease-causing bugs, allergens or pollutants
to slip by. But Johns Hopkins researchers
have discovered a way to chemically shrink the holes in the
mucus layer's netting so that it will keep
out more of the unwanted particles.
"The mucus layer is an outstanding barrier to most
things but not a perfect one for objects
smaller than several hundred nanometers [about 1,000 times
smaller than the width a human hair]. We
still get sick far too often," said Samuel Lai, a chemical
and biomolecular researcher in the Whiting
School of Engineering and a member of the university's
"The question we asked was, Can we shrink the size of
the holes in the human mucus barrier to
help prevent its penetration by potentially harmful
nano-size objects?" said Justin Hanes, principal
investigator of the study and a professor of
biomolecular engineering. Hanes also is
director of therapeutics for the INBT.
The team showed that tiny strands in the mucus layer
— the mucin fibers — naturally tend to
bundle and bunch together, creating gaps large enough for
pathogens and potentially dangerous
pollutants to get in. But by adding a simple detergent to
the mix, Lai and his colleagues partially
disrupted the bundling of mucin fibers, a procedure that
decreased the size of the holes in the mesh.
Particles in the range of 200 nanometers in diameter that
previously slipped through easily now
became trapped in the more finely strung netting.
The findings were reported in the Jan. 28 online
edition of the journal Public Library of Science
For this research, the team studied protective
coatings taken from the female reproductive
tract, conducting high-resolution microscopy experiments
with particles as large as 1 micron and as
small as 100 nanometers in size.
To shrink the holes in the network's mesh, the
researchers used a detergent commonly found in
many personal care products. Mucus treated with the
detergent slowed nanoparticle movement
dramatically, especially in the 200-500 nanometer range,
which was clearly demonstrated in videos
enhanced by fluorescent imaging.
"We suspected the fibers are bundled together, making
large holes in the mucus mesh, but this
was the first time it was shown definitively," said
Ying-Ying Wang, a doctoral student and National
Science Foundation graduate fellowship recipient in
biomedical engineering. "And we didn't know going
into this study exactly how much we could shrink the holes,
if at all. It was exciting to see particles
the size of many potentially dangerous substances become
completely trapped in mucus, since mucus
trapping typically leads to harmless removal from our
bodies," Wang added.
The team, which also includes Richard Cone, a biophysics
professor and INBT-affiliated faculty
member from the Krieger School of Arts and Sciences, and
Denis Wirtz, professor of chemical and
biomolecular engineering in the Whiting School and INBT's
associate director, envisions many potential
applications for this concept.
"If there is an outbreak of influenza, for example, we
imagine that doctors and nurses could
inhale these agents in an aerosolized form and be protected
against the virus for several hours," Lai
said. "People who work where there are high levels of
nanoparticles in the air, such as mine workers or
builders, could use a product with these fiber debundling
detergents to prevent dangerous exposure."
Since the mucus layer constantly clears from the body,
any enhancement to its protective
ability would be short-lived, added Lai. For example,
coatings clear from the lungs in as little as 30
minutes, while the mucus lining in the stomach and
intestine takes several hours to renew.
This study is only a start, Lai said, and the
technique has not yet been tested in humans. "The
next step will be to try different substances, perhaps
those paired to specific pathogens, and observe
how these substances improve the performance of the mucus
barrier," he said. In addition, microbe-
killing agents could be combined with detergents to not
only slow but destroy the trapped potential
pathogens, he said. Animal studies are being planned.
This work was funded by the National Institutes of
Health and a graduate research fellowship
from the National Science Foundation.