Cell
membrane researchers are eagerly bracing for a long-awaited
cold wave. A new partnership involving the National Institute
of Standards and Technology (NIST), the University of California-Irvine
(UCI) and other organizations will use beams of super-chilled
neutrons to probe the elusive structure and interactions
of cell membranes and their components, gathering information
key to improving disease diagnosis and treatment.
Led
by UCI biophysicist Stephen White, the Cold Neutrons for
Biology and Technology (CNBT) team received $5 million from
the National Center for Research Resources of the National
Institutes of Health to build the nation's first neutron-beam
research station fully dedicated to biological membrane
experiments. To be located at the NIST Center for Neutron
Research (NCNR) in Gaithersburg, Md., the CNBT team will
exploit the NIST center's ability to generate high-quality
beams of "cold" neutrons. Stripped from the nuclei
of heavy atoms and then cooled by liquid hydrogen, these
uncharged particles are ideally suited for exploring the
disordered, continually changing landscape of cell membranes.
"Cold
neutrons provide a powerful tool for studying cell membrane
systems," says White, "but the demand for beam
time at the handful of neutron facilities in the United
States is so great that the tool was nearly unavailable
for this kind of research. Yet, for many challenges in biology
and medicine, neutron probes offer the only realistic hope
for answers."
For
example, White says that only neutron probes can glimpse
the process by which protein fragments, or peptides, are
assembled into membrane-borne sentries that ward off harmful
microorganisms.
To ease
the neutron crunch for biologists, NIST offered to open
a new port in a beamline at its NCNR. White then organized
the CNBT partnership, which includes researchers from UCI,
NIST, the University of Pennsylvania, Rice University, Carnegie
Mellon University, the Duke University Medical Center and
the Los Alamos National Laboratory.
Neutrons are non-destructive, highly penetrating probes,
valuable for studying changes in membranes over time. Because
they behave like tiny waves of energy, neutrons also make
excellent rulers. Depending on temperature, the length of
the neutron ruler can be tuned over a range spanning from
roughly the size of a single atom to the size of a molecule
composed of hundreds or thousands of atoms.
The
CNBT team is now building a unique instrument with dual
capabilities: diffractometry and reflectometry. It will
detect neutrons that are reflected or otherwise scattered
after striking membrane samples. Reflected or diffracted
neutrons will provide information on the location, orientation,
size and composition of membrane components. In addition,
the team is upgrading another instrument useful for studying
large molecules--a small-angle neutron spectrometer--that
will be shared with researchers in other fields.
The
instruments are scheduled to be completed in 2003. They
will provide cell membrane scientists with access to powerful
technologies well beyond the resources of individual researchers.
"This
is an extremely hard problem," says NIST biophysicist
Susan Krueger, a CNBT collaborator interested in enhancing
neutron-based measurement capabilities. "We'll be testing
lots of membrane systems and lots of different approaches
to capturing the data we need."
The
job facing cell-membrane researchers is akin to assembling
an intricate and dynamic three-dimensional puzzle. Many
pieces have complex contours that not only are unknown but
also are subject to change.
"No
single instrument or set of techniques can supply all the
missing information," says NIST's Krueger. In addition
to neutron scattering, an array of other tools and methods--X-rays,
nuclear magnetic resonance and many more--is required.
Ultimately,
the team hopes to use painstakingly gathered experimental
data to predict molecular structure and the course of cell-membrane
interactions. Computer models already are under development.
For example, UCI chemistry professor Douglas Tobias is working
on a computer simulation that can provide three-dimensional
images and may even show changes in membrane structure over
time.
"We
aim to close a big gap in our understanding of cell-membrane
biology," White says.
As
a non-regulatory agency of the U.S. Department of Commerce's
Technology Administration, NIST develops and promotes measurement,
standards, and technology to enhance productivity, facilitate
trade, and improve the quality of life.
NOTE
TO EDITORS: Brief descriptions of the research interests
of scientists participating in the CNBT collaboration--along
with information on NIST's Center for Neutron Research--are
available at: www.nist.gov/public_affairs/releases/neutrons.htm.
For information on images of cell membranes and cell-membrane
proteins, contact UCI's Andrew Porterfield, amporter@uci.edu;
(949) 824-3969.
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