Materials scientists working with biologists at the University of California,
Santa Barbara have developed "smart" bio-nanotubes — with open or closed ends — that
could be developed for drug or gene delivery applications.
The nanotubes are "smart" because in the future they could be designed to encapsulate
and then open up to deliver a drug or gene in a particular location in the body.
The scientists found that by manipulating the electrical charges of lipid bilayer
membranes and microtubules from cells, they could create open or closed bio-nanotubes,
or nanoscale capsules.The news is reported in an article to be published August
9 issue of the Proceedings of the National Academy of Sciences. It is currently
available on-line in the PNAS Early Edition.
The findings resulted from a collaboration between
the laboratories of Cyrus R. Safinya, professor of
materials and physics and faculty member of the Molecular,
Cellular, and Developmental Biology Department, and
Leslie Wilson, professor of biochemistry in the Department
of Molecular, Cellular and Developmental Biology
and the Biomolecular Science and Engineering Program.
The first author of the article is Uri Raviv, a post-doctoral
researcher in Safinya's lab and a fellow of the International
Human Frontier Science Program Organization. The
other co-authors are: Daniel J. Needleman, formerly
Safinya's graduate student who is now a postdoctoral
fellow at Harvard Medical School; Youli Li, researcher
in the Materials Research Laboratory; and Herbert
P. Miller, staff research associate in the Department
of Molecular, Cellular and Developmental Biology.
The scientists used microtubules purified from the brain tissue of a cow for
their experiments. Microtubules are nanometer-scale hollow cylinders derived
from the cell cytoskeleton. In an organism, microtubules and their assembled
structures are critical components in a broad range of cell functions –– from
providing tracks for the transport of cargo to forming the spindle structure
in cell division. Their functions include the transport of neurotransmitter precursors
"In our paper, we report on a new paradigm for lipid self-assembly leading to
nanotubule formation in mixed charged systems," said Safinya.
Raviv explained, "We looked at the interaction between microtubules –– negatively
charged nanometer-scale hollow cylinders derived from cell cytoskeleton –– and
cationic (positively charged) lipid membranes. We discovered that, under the
right conditions, spontaneous lipid protein nanotubules will form."
They used the example of water beading up or coating a car, depending on whether
or not the car has been waxed. Likewise the lipid will either bead up on the
surface of the microtubule, or flatten out and coat the whole cylindrical surface
of the microtubule, depending on the charge.
The new type of self-assembly arises because of an extreme mismatch between the
charge densities of microtubules and cationic lipid, explained Raviv. "This is
a novel finding in equilibrium self-assembly," he said.
The nanotubule consisting of a three-layer wall appears to be the way the system
compensates for this charge density mismatch, according to the authors.
"Very interestingly, we have found that controlling the degree of overcharging
of the lipid-protein nanotube enables us to switch between two states of nanotubes," said
Safinya. "With either open ends (negative overcharged), or closed ends (positive
overcharged with lipid caps), these nanotubes could form the basis for controlled
chemical and drug encapsulation and release."
The inner space of the nanotube in these experiments measures about 16 nanometers
in diameter. (A nanometer is a billionth of a meter.) The whole capsule is about
40 nanometers in diameter.
Raviv explained that the chemotherapy drug Taxol is one type of drug that could
be delivered with these nanotubes. The scientists are already using Taxol in
their experiments to stabilize and lengthen the lipid-protein nanotubes.
The work was performed using state-of-the-art synchrotron x-ray scattering techniques
at the Stanford Synchrotron Radiation Laboratory (SSRL), combined with sophisticated
electron microscopy at UCSB. The work was funded by the National Institutes of
Health and the National Science Foundation. SSRL is supported by the U.S. Department
of Energy. Raviv was also supported by the International Human Frontier Science
Program and the European Molecular Biology Organization.
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