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Biological Chemistry

On the Ball

Lipid-coated beads used to detect binding events at membrane surfaces

by Amanda Yarnell
January 12, 2004 | A version of this story appeared in Volume 82, Issue 2

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Click image to see the membrane-coated glass beads in their condensed--but still very dynamic--two-dimensional colloid phase.
Click image to see the membrane-coated glass beads in their condensed--but still very dynamic--two-dimensional colloid phase.

Many important cellular processes occur at membrane surfaces, and many drugs and infectious disease agents target proteins in cell membranes. Studying these poorly understood processes may soon get easier, thanks to a new technique for detecting binding events that occur at membrane surfaces.

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Click image to see them in their dispersed colloid phase, a transition that was triggered by addition of a protein antibody that binds to a ligand embedded in the membrane.
Click image to see them in their dispersed colloid phase, a transition that was triggered by addition of a protein antibody that binds to a ligand embedded in the membrane.

The method, developed by University of California, Berkeley, assistant professor of chemistry Jay T. Groves, depends on coating microscopic silica beads with a phospholipid bilayer [Nature, 427, 139 (2004)]. The fluidity of the bead-supported bilayer mimics that of natural cell membranes, and it's simple to embed fully functional ligands or protein receptors.

When dispersed in water, these membrane-coated beads spontaneously form two-dimensional colloidal crystals. The beads' order is disrupted, however, when a protein receptor that binds to a ligand in the membrane is added to the solution. The dynamic process can be observed under a conventional light microscope.

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Credit: COURTESY OF JAY GROVES
Microscopic glass beads coated with lipid membranes containing tiny amounts of a ligand tend to clump together in aqueous solution (above left; purple halos mark the edge of each bead). When the ligand's protein receptor is added, the beads disperse (right).
Credit: COURTESY OF JAY GROVES
Microscopic glass beads coated with lipid membranes containing tiny amounts of a ligand tend to clump together in aqueous solution (above left; purple halos mark the edge of each bead). When the ligand's protein receptor is added, the beads disperse (right).

But direct observation of the process isn't necessary, Groves notes. His team uses statistical methods to track changes in the spatial order of the beads. They're now working to adapt the method for high-throughput screening for protein-ligand interactions on membrane surfaces.

Biophysicist Thomas M. Bayerl of the University of Würzburg, in Germany, calls the study a "promising start," noting that Groves's method allows sensitive and specific detection of molecular interactions at the membrane surface. And unlike other methods, it doesn't require fluorescent labels or sophisticated techniques. But it remains to be seen how general the new method is, he says.

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