LOUIS -- The tumblers of life continue to click
as Cornell University researchers have fabricated
a set of "nano-keys" on
the molecular scale to interact with receptors
on cell membranes and trigger larger-scale responses
within cells -- such as the release of histamines
in an allergic response.
How cell membranes control cellular function has
long been studied but with ambiguous results. However,
nanotechnology now gives researchers new tools to
understand the role of cell membranes in activating
responses within cells.
Barbara Baird, Cornell professor of chemistry and
chemical biology, reported this research today (Feb.16)
at the annual meeting of the American Association
for the Advancement of Science. She is the director
of Cornell's Nanobiotechnology Center, which is funded
by the National Science Foundation.
One day, Baird said, scientists might use these
insights to develop new drug therapies for allergies
and other immune responses, high cholesterol and
perhaps viral infections.
By understanding a membrane's role in cell function,
she explained that these nano-keys could interfere
with responses via the membrane interactions, rather
than just targeting proteins to block responses.
This could lead to designing ligands (molecules that
bind to receptors) that trigger a desired response
or inhibit an allergic reaction and preventing the
release of histamines and other inflammatory mediators.
her presentation, "Design and Fabrication of
Stimuli to Reveal Spatial Regulation of Cellular
Signaling," she explained, "We want to understand
how the receptors on cell surfaces mediate cellular
responses, how cells work on a molecular level."
To study how receptors on cell membranes jump-start
cellular responses, Baird and her colleagues chose
to work with mast cells. They were chosen because
mast cells secrete chemicals and histamines (substances
released in allergic reactions that cause runny nose,
watery eyes and other characteristic allergy symptoms)
and they are the gatekeepers for the allergic immune
response. This system can be manipulated experimentally.
Specifically, Baird works with immunoglobulin E
(IgE) antibodies, which mount membrane proteins on
mast cells to form receptor complexes that sense
the environment and sensitize the cell to allergens,
which are substances that cause an allergic reaction.
Typically, two or more receptors cluster together
when they bind with an antigen (allergen or foreign
body), and this causes transmembrane activation of
enzymes within the cell that eventually lead to the
release of histamines.
Such processes begin on the nanoscale (a nanometer
equals one-billionth of a meter) -- at the molecular
level on the cell's surface and lead to a system-wide
response. At present, very little is known about
the structural changes caused by receptor clustering
that allow cells to sense their outer environment
and start cellular processes within the cell.
The so-called nano-keys are surfaces of silicon
with a layer of polymer or a thin lipid (fatty molecules
that make up cell membranes) bilayer. The surfaces,
which are engineered on the micron scale (0.000001
meter; there are 25,400 microns in an inch), are
arranged in patterns that contain antigens and cause
IgE-receptors to cluster when the cells attach to
the surface. This activates the cell's inner machinery.
this way, we can control what the cell sees. The
cells are binding to the engineered surfaces and
getting turned on. We can then see how the cell
is organizing itself due to the stimulus."
Collaborators include: David Holowka, Cornell senior
scientist in chemistry; and the research groups of
Harold G. Craighead, Cornell professor of applied
and engineering physics; Dan Luo, Cornell assistant
professor of biological and environmental engineering;
Christopher Ober, Cornell professor of materials
science and engineering; Watt Webb, Cornell's Eckert
Professor in Engineering; and Ulrich Wiesner, Cornell
professor of materials science and engineering.
Contact: Blaine Friedlander
Office: (607) 254-8093