Scientists at Stanford University have done the next best thing to packaging
living cells in individual boxes for study.
Borrowing microfabrication techniques from electrical engineering, the
researchers have created a specially prepared surface that holds millions
of cell-sized squares, or "corrals," composed of an artificial
membrane that closely mimics the surface of living cells. According to
the researchers, the ability to work with these independent membranes that
are uniform in size and fixed in space makes many new experiments possible.
The work, coauthored by graduate student Jay T. Groves, chemistry Professor
Steven G. Boxer, and Ginzton Laboratory research associate Nick Ulman,
is reported in the January 31st issue of Science.
According to the scientists, not only are the micro-membranes likely
to become an important research tool but the system also could serve as
the basis for improved cell and drug screening methods because it is ideally
suited for automation.
Determining the Structure of Membrane Proteins
One possible application of these micromembranes is as a tool for determining
the structure of membrane proteins.
One powerful method for determining the structure of proteins is x-ray
crystallography. For this method to work, however, researchers must purify
and crystallize the material. This has proven very difficult for proteins
associated with membranes because they cannot be easily separated from
the membrane material.
According to Boxer, the new method may help overcome this difficulty.
Many associated proteins can move freely on a membrane's surface. In previous
work, the researchers demonstrated that they can use electric fields to
concentrate such proteins against two-dimensional membrane boundaries.
It may be possible to both concentrate and crystallize such proteins by
applying an intense electrical field. If so, the method could be used with
existing techniques to determine the two-dimensional structure of groups
of membrane proteins and with x-ray crystallography to identify the three-dimensional
structures of some of these compounds.
Potential Biomedical Application
A potential biomedical application is cell screening of the type required
for leukemia patients. Doctors must closely monitor the different kinds
of cells in a leukemia patient's blood. Using a small wafer holding millions
of micropatches that have been seeded with proteins that bind to different
kinds of cells, it should be possible to obtain measurements of the relative
numbers of different cell types by simply covering the wafer with blood,
washing it off, and counting the cells that remain stuck to different patches.
Not only could this method identify and separate different kinds of cells
(like current methods), but also it potentially could measure how well
the cells are functioning, Groves suggested.
In a similar fashion, the technique might be used to screen for drugs,
such as channel blockers, that interact with receptors on a cell's surface
and interior membranes, the researchers said.
"We have developed something new at the interface between cell
science, chemistry and electrical engineering that has widespread potential
in many areas," Boxer said.