Researchers Corral Millions of Microscopic Membranes

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.