An experiment that began as a “fantasy pipe dream” just three years ago is now a reality. Researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley, combining nanotechnology with biochemistry, have created unique synthetic membranes that, for the first time ever, enable them to directly control signaling activity in living T cells from the immune system. Already their experiments have yielded surprising results.
These fluorescently labeled electron micrographs show immunological synapses formed by T cell receptors (green) and adhesion molecules (red). Image (A) shows the synapse in its natural bull’s eye shape; in image (B) chromium lines were used to pattern the synapse with parallel lines; (C) the synapse was patterned into a square grid; and (D), the synapse was patterned into concentric hexagons.
This watercolor painting by Raghuveer Parthasarathy, a member of Jay Groves research group, shows a hybrid interface between a living T cell and a synthetic membrane on a substrate that has been patterned with chromium lines. T cell receptors (TCRs) are communicating with their corresponding signaling ligands on the membrane. By controlling the spatial arrangements of the signaling ligands, scientists can control the T cell’s overall response.
“This marriage of inorganic nanotechnology with organic molecules and cells enables us to go inside a living cell and physically move around its signaling molecules with molecular precision,” said Jay Groves, a chemist who holds a joint appointment with Berkeley Lab’s Physical Biosciences Division and UC Berkeley’s Chemistry Department. “Our experimental beaker has now become the inside of living cells and we can watch chemical reactions take place there.”
Groves is the principal co-author, along with Michael Dustin, a cellular immunologist at New York University (NYU), of a paper published in the November 18, 2005 issue of the journal Science, entitled: “Altered TCR Signaling from Geometrically Repatterned Immunological Synapses.” The lead author is Kaspar Mossman, a graduate student in Groves’ research group, and the second co-author is Gabriele Campi, a graduate student at NYU with Dustin.
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